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<StructureSection load='3qb4' size='340' side='right'caption='[[3qb4]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
<StructureSection load='3qb4' size='340' side='right'caption='[[3qb4]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3qb4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QB4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3qb4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QB4 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3evs|3evs]], [[1rew|1rew]], [[1waq|1waq]], [[2k3g|2k3g]], [[3nh7|3nh7]]</div></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.28&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDMP1, GDF5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ACVRLK3, ALK3, BMPR1A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb4 OCA], [https://pdbe.org/3qb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qb4 RCSB], [https://www.ebi.ac.uk/pdbsum/3qb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qb4 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb4 OCA], [https://pdbe.org/3qb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qb4 RCSB], [https://www.ebi.ac.uk/pdbsum/3qb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qb4 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[https://www.uniprot.org/uniprot/GDF5_HUMAN GDF5_HUMAN]] Defects in GDF5 are the cause of acromesomelic chondrodysplasia Grebe type (AMDG) [MIM:[https://omim.org/entry/200700 200700]]. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs, and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMDG is an autosomal recessive form characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.<ref>PMID:9288098</ref>  Defects in GDF5 are the cause of acromesomelic chondrodysplasia Hunter-Thompson type (AMDH) [MIM:[https://omim.org/entry/201250 201250]]. AMDH is an autosomal recessive form of dwarfism. Patients have limb abnormalities, with the middle and distal segments being most affected and the lower limbs more affected than the upper. AMDH is characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.  Defects in GDF5 are the cause of brachydactyly type C (BDC) [MIM:[https://omim.org/entry/113100 113100]]. BDC is an autosomal dominant disorder characterized by an abnormal shortness of the fingers and toes. Note=Some BDC patients with GDF5 mutations also manifest clinical features of ASPED angel-shaped phalango-epiphyseal dysplasia (ASPED), an autosomal dominant skeletal abnormality characterized by a typical angel-shaped phalanx, brachydactyly, specific radiological findings, abnormal dentition, hip dysplasia, and delayed bone age. This suggests that BDC and ASPED are part of the same clinical spectrum (PubMed:22828468).<ref>PMID:22828468</ref> <ref>PMID:14735582</ref>  Defects in GDF5 are the cause of Du Pan syndrome (DPS) [MIM:[https://omim.org/entry/228900 228900]]; also known as fibular hypoplasia and complex brachydactyly. Du Pan syndrome is a rare autosomal recessive condition characterized by absence of the fibulae and severe acromesomelic limb shortening with small, non-functional toes. Although milder, the phenotype resembles the autosomal recessive Hunter-Thompson and Grebe types of acromesomelic chondrodysplasia.<ref>PMID:12121354</ref> <ref>PMID:16222676</ref> <ref>PMID:18629880</ref>  Defects in GDF5 are a cause of symphalangism proximal syndrome (SYM1) [MIM:[https://omim.org/entry/185800 185800]]. SYM1 is characterized by the hereditary absence of the proximal interphalangeal (PIP) joints (Cushing symphalangism). Severity of PIP joint involvement diminishes towards the radial side. Distal interphalangeal joints are less frequently involved and metacarpophalangeal joints are rarely affected whereas carpal bone malformation and fusion are common. In the lower extremities, tarsal bone coalition is common. Conducive hearing loss is seen and is due to fusion of the stapes to the petrous part of the temporal bone.<ref>PMID:16127465</ref> <ref>PMID:16892395</ref> <ref>PMID:18283415</ref>  Defects in GDF5 are the cause of multiple synostoses syndrome type 2 (SYNS2) [MIM:[https://omim.org/entry/610017 610017]]. Multiple synostoses syndrome is an autosomal dominant condition characterized by progressive joint fusions of the fingers, wrists, ankles and cervical spine, characteristic facies and progressive conductive deafness.[:]<ref>PMID:16532400</ref>  Defects in GDF5 are a cause of brachydactyly type A2 (BDA2) [MIM:[https://omim.org/entry/112600 112600]]. Brachydactylies (BDs) are a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. They have been classified on an anatomic and genetic basis into five groups, A to E, including three subgroups (A1 to A3) that usually manifest as autosomal dominant traits.<ref>PMID:16127465</ref> <ref>PMID:18203755</ref>  Genetic variations in GDF5 are associated with susceptibility to osteoarthritis type 5 (OS5) [MIM:[https://omim.org/entry/612400 612400]]. Osteoarthritis is a degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement.  Defects in GDF5 may be a cause of brachydactyly type A1 (BDA1) [MIM:[https://omim.org/entry/112500 112500]]. Brachydactylies (BDs) are a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. They have been classified on an anatomic and genetic basis into five groups, A to E, including three subgroups (A1 to A3) that usually manifest as autosomal dominant traits.<ref>PMID:20683927</ref> [[https://www.uniprot.org/uniprot/BMR1A_HUMAN BMR1A_HUMAN]] Defects in BMPR1A are a cause of juvenile polyposis syndrome (JPS) [MIM:[https://omim.org/entry/174900 174900]]; also known as juvenile intestinal polyposis (JIP). JPS is an autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers.<ref>PMID:11381269</ref> <ref>PMID:11536076</ref> <ref>PMID:12417513</ref> <ref>PMID:12136244</ref> <ref>PMID:12630959</ref>  Defects in BMPR1A are a cause of Cowden disease (CD) [MIM:[https://omim.org/entry/158350 158350]]. CD is an autosomal dominant cancer syndrome characterized by multiple hamartomas and by a high risk for breast, thyroid and endometrial cancers.<ref>PMID:11381269</ref> <ref>PMID:11536076</ref>  Defects in BMPR1A are the cause of hereditary mixed polyposis syndrome 2 (HMPS2) [MIM:[https://omim.org/entry/610069 610069]]. Hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas.<ref>PMID:11381269</ref>  Note=A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.<ref>PMID:11381269</ref> 
[https://www.uniprot.org/uniprot/GDF5_HUMAN GDF5_HUMAN] Defects in GDF5 are the cause of acromesomelic chondrodysplasia Grebe type (AMDG) [MIM:[https://omim.org/entry/200700 200700]. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs, and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMDG is an autosomal recessive form characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.<ref>PMID:9288098</ref>  Defects in GDF5 are the cause of acromesomelic chondrodysplasia Hunter-Thompson type (AMDH) [MIM:[https://omim.org/entry/201250 201250]. AMDH is an autosomal recessive form of dwarfism. Patients have limb abnormalities, with the middle and distal segments being most affected and the lower limbs more affected than the upper. AMDH is characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.  Defects in GDF5 are the cause of brachydactyly type C (BDC) [MIM:[https://omim.org/entry/113100 113100]. BDC is an autosomal dominant disorder characterized by an abnormal shortness of the fingers and toes. Note=Some BDC patients with GDF5 mutations also manifest clinical features of ASPED angel-shaped phalango-epiphyseal dysplasia (ASPED), an autosomal dominant skeletal abnormality characterized by a typical angel-shaped phalanx, brachydactyly, specific radiological findings, abnormal dentition, hip dysplasia, and delayed bone age. This suggests that BDC and ASPED are part of the same clinical spectrum (PubMed:22828468).<ref>PMID:22828468</ref> <ref>PMID:14735582</ref>  Defects in GDF5 are the cause of Du Pan syndrome (DPS) [MIM:[https://omim.org/entry/228900 228900]; also known as fibular hypoplasia and complex brachydactyly. Du Pan syndrome is a rare autosomal recessive condition characterized by absence of the fibulae and severe acromesomelic limb shortening with small, non-functional toes. Although milder, the phenotype resembles the autosomal recessive Hunter-Thompson and Grebe types of acromesomelic chondrodysplasia.<ref>PMID:12121354</ref> <ref>PMID:16222676</ref> <ref>PMID:18629880</ref>  Defects in GDF5 are a cause of symphalangism proximal syndrome (SYM1) [MIM:[https://omim.org/entry/185800 185800]. SYM1 is characterized by the hereditary absence of the proximal interphalangeal (PIP) joints (Cushing symphalangism). Severity of PIP joint involvement diminishes towards the radial side. Distal interphalangeal joints are less frequently involved and metacarpophalangeal joints are rarely affected whereas carpal bone malformation and fusion are common. In the lower extremities, tarsal bone coalition is common. Conducive hearing loss is seen and is due to fusion of the stapes to the petrous part of the temporal bone.<ref>PMID:16127465</ref> <ref>PMID:16892395</ref> <ref>PMID:18283415</ref>  Defects in GDF5 are the cause of multiple synostoses syndrome type 2 (SYNS2) [MIM:[https://omim.org/entry/610017 610017]. Multiple synostoses syndrome is an autosomal dominant condition characterized by progressive joint fusions of the fingers, wrists, ankles and cervical spine, characteristic facies and progressive conductive deafness.[:]<ref>PMID:16532400</ref>  Defects in GDF5 are a cause of brachydactyly type A2 (BDA2) [MIM:[https://omim.org/entry/112600 112600]. Brachydactylies (BDs) are a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. They have been classified on an anatomic and genetic basis into five groups, A to E, including three subgroups (A1 to A3) that usually manifest as autosomal dominant traits.<ref>PMID:16127465</ref> <ref>PMID:18203755</ref>  Genetic variations in GDF5 are associated with susceptibility to osteoarthritis type 5 (OS5) [MIM:[https://omim.org/entry/612400 612400]. Osteoarthritis is a degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement.  Defects in GDF5 may be a cause of brachydactyly type A1 (BDA1) [MIM:[https://omim.org/entry/112500 112500]. Brachydactylies (BDs) are a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. They have been classified on an anatomic and genetic basis into five groups, A to E, including three subgroups (A1 to A3) that usually manifest as autosomal dominant traits.<ref>PMID:20683927</ref>  
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/GDF5_HUMAN GDF5_HUMAN]] Could be involved in bone and cartilage formation. Chondrogenic signaling is mediated by the high-affinity receptor BMPR1B.<ref>PMID:15530414</ref> <ref>PMID:19229295</ref>  [[https://www.uniprot.org/uniprot/BMR1A_HUMAN BMR1A_HUMAN]] On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP-2 and BMP-4.
[https://www.uniprot.org/uniprot/GDF5_HUMAN GDF5_HUMAN] Could be involved in bone and cartilage formation. Chondrogenic signaling is mediated by the high-affinity receptor BMPR1B.<ref>PMID:15530414</ref> <ref>PMID:19229295</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: Bone morphogenetic protein (BMP)-2 and growth and differentiation factor (GDF)-5 are two related transforming growth factor (TGF)-beta family members with important functions in embryonic development and tissue homeostasis. BMP-2 is best known for its osteoinductive properties whereas GDF-5-as evident from its alternative name, cartilage derived morphogenetic protein 1-plays an important role in the formation of cartilage. In spite of these differences both factors signal by binding to the same subset of BMP receptors, raising the question how these different functionalities are generated. The largest difference in receptor binding is observed in the interaction with the type I receptor BMPR-IA. GDF-5, in contrast to BMP-2, shows preferential binding to the isoform BMPR-IB, which is abrogated by a single amino acid (A57R) substitution. The resulting variant, GDF-5 R57A, represents a "BMP-2 mimic" with respect to BMP receptor binding. In this study we thus wanted to analyze whether the two growth factors can induce distinct signals via an identically composed receptor. RESULTS: Unexpectedly and dependent on the cellular context, GDF-5 R57A showed clear differences in its activity compared to BMP-2. In ATDC-5 cells, both ligands induced alkaline phosphatase (ALP) expression with similar potency. But in C2C12 cells, the BMP-2 mimic GDF-5 R57A (and also wild-type GDF-5) clearly antagonized BMP-2-mediated ALP expression, despite signaling in both cell lines occurring solely via BMPR-IA. The BMP-2- antagonizing properties of GDF-5 and GDF-5 R57A could also be observed in vivo when implanting BMP-2 and either one of the two GDF-5 ligands simultaneously at heterotopic sites. CONCLUSIONS: Although comparison of the crystal structures of the GDF-5 R57A:BMPR-IAEC- and BMP-2:BMPR-IAEC complex revealed small ligand-specific differences, these cannot account for the different signaling characteristics because the complexes seem identical in both differently reacting cell lines. We thus predict an additional component, most likely a not yet identified GDF-5-specific co-receptor, which alters the output of the signaling complexes. Hence the presence or absence of this component then switches GDF-5's signaling capabilities to act either similar to BMP-2 or as a BMP-2 antagonist. These findings might shed new light on the role of GDF-5, e.g., in cartilage maintenance and/or limb development in that it might act as an inhibitor of signaling events initiated by other BMPs.
 
GDF-5 can act as a context-dependent BMP-2 antagonist.,Klammert U, Mueller TD, Hellmann TV, Wuerzler KK, Kotzsch A, Schliermann A, Schmitz W, Kuebler AC, Sebald W, Nickel J BMC Biol. 2015 Sep 18;13(1):77. doi: 10.1186/s12915-015-0183-8. PMID:26385096<ref>PMID:26385096</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3qb4" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Receptor protein serine/threonine kinase]]
[[Category: Mueller TD]]
[[Category: Mueller, T D]]
[[Category: Nickel J]]
[[Category: Nickel, J]]
[[Category: Sebald W]]
[[Category: Sebald, W]]
[[Category: Cystine-knot]]
[[Category: Cytokine-transferase receptor complex]]
[[Category: Ligand-receptor complex]]
[[Category: Membrane/extracellular]]
[[Category: Protein]]

Revision as of 14:39, 14 March 2024

Crystal structure of a TGF-beta ligand-receptor complexCrystal structure of a TGF-beta ligand-receptor complex

Structural highlights

3qb4 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.28Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GDF5_HUMAN Defects in GDF5 are the cause of acromesomelic chondrodysplasia Grebe type (AMDG) [MIM:200700. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs, and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMDG is an autosomal recessive form characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.[1] Defects in GDF5 are the cause of acromesomelic chondrodysplasia Hunter-Thompson type (AMDH) [MIM:201250. AMDH is an autosomal recessive form of dwarfism. Patients have limb abnormalities, with the middle and distal segments being most affected and the lower limbs more affected than the upper. AMDH is characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet. Defects in GDF5 are the cause of brachydactyly type C (BDC) [MIM:113100. BDC is an autosomal dominant disorder characterized by an abnormal shortness of the fingers and toes. Note=Some BDC patients with GDF5 mutations also manifest clinical features of ASPED angel-shaped phalango-epiphyseal dysplasia (ASPED), an autosomal dominant skeletal abnormality characterized by a typical angel-shaped phalanx, brachydactyly, specific radiological findings, abnormal dentition, hip dysplasia, and delayed bone age. This suggests that BDC and ASPED are part of the same clinical spectrum (PubMed:22828468).[2] [3] Defects in GDF5 are the cause of Du Pan syndrome (DPS) [MIM:228900; also known as fibular hypoplasia and complex brachydactyly. Du Pan syndrome is a rare autosomal recessive condition characterized by absence of the fibulae and severe acromesomelic limb shortening with small, non-functional toes. Although milder, the phenotype resembles the autosomal recessive Hunter-Thompson and Grebe types of acromesomelic chondrodysplasia.[4] [5] [6] Defects in GDF5 are a cause of symphalangism proximal syndrome (SYM1) [MIM:185800. SYM1 is characterized by the hereditary absence of the proximal interphalangeal (PIP) joints (Cushing symphalangism). Severity of PIP joint involvement diminishes towards the radial side. Distal interphalangeal joints are less frequently involved and metacarpophalangeal joints are rarely affected whereas carpal bone malformation and fusion are common. In the lower extremities, tarsal bone coalition is common. Conducive hearing loss is seen and is due to fusion of the stapes to the petrous part of the temporal bone.[7] [8] [9] Defects in GDF5 are the cause of multiple synostoses syndrome type 2 (SYNS2) [MIM:610017. Multiple synostoses syndrome is an autosomal dominant condition characterized by progressive joint fusions of the fingers, wrists, ankles and cervical spine, characteristic facies and progressive conductive deafness.[:][10] Defects in GDF5 are a cause of brachydactyly type A2 (BDA2) [MIM:112600. Brachydactylies (BDs) are a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. They have been classified on an anatomic and genetic basis into five groups, A to E, including three subgroups (A1 to A3) that usually manifest as autosomal dominant traits.[11] [12] Genetic variations in GDF5 are associated with susceptibility to osteoarthritis type 5 (OS5) [MIM:612400. Osteoarthritis is a degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement. Defects in GDF5 may be a cause of brachydactyly type A1 (BDA1) [MIM:112500. Brachydactylies (BDs) are a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. They have been classified on an anatomic and genetic basis into five groups, A to E, including three subgroups (A1 to A3) that usually manifest as autosomal dominant traits.[13]

Function

GDF5_HUMAN Could be involved in bone and cartilage formation. Chondrogenic signaling is mediated by the high-affinity receptor BMPR1B.[14] [15]

See Also

References

  1. ↑ Thomas JT, Kilpatrick MW, Lin K, Erlacher L, Lembessis P, Costa T, Tsipouras P, Luyten FP. Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1. Nat Genet. 1997 Sep;17(1):58-64. PMID:9288098 doi:10.1038/ng0997-58
  2. ↑ Gutierrez-Amavizca BE, Brambila-Tapia AJ, Juarez-Vazquez CI, Holder-Espinasse M, Manouvrier-Hanu S, Escande F, Barros-Nunez P. A novel mutation in CDMP1 causes brachydactyly type C with "angel-shaped phalanx". A genotype-phenotype correlation in the mutational spectrum. Eur J Med Genet. 2012 Nov;55(11):611-4. doi: 10.1016/j.ejmg.2012.07.004. Epub, 2012 Jul 22. PMID:22828468 doi:10.1016/j.ejmg.2012.07.004
  3. ↑ Schwabe GC, Turkmen S, Leschik G, Palanduz S, Stover B, Goecke TO, Mundlos S. Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1. Am J Med Genet A. 2004 Feb 1;124A(4):356-63. PMID:14735582 doi:10.1002/ajmg.a.20349
  4. ↑ Faiyaz-Ul-Haque M, Ahmad W, Zaidi SH, Haque S, Teebi AS, Ahmad M, Cohn DH, Tsui LC. Mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene in a kindred affected with fibular hypoplasia and complex brachydactyly (DuPan syndrome). Clin Genet. 2002 Jun;61(6):454-8. PMID:12121354
  5. ↑ Szczaluba K, Hilbert K, Obersztyn E, Zabel B, Mazurczak T, Kozlowski K. Du Pan syndrome phenotype caused by heterozygous pathogenic mutations in CDMP1 gene. Am J Med Genet A. 2005 Nov 1;138(4):379-83. PMID:16222676 doi:10.1002/ajmg.a.30969
  6. ↑ Douzgou S, Lehmann K, Mingarelli R, Mundlos S, Dallapiccola B. Compound heterozygosity for GDF5 in Du Pan type chondrodysplasia. Am J Med Genet A. 2008 Aug 15;146A(16):2116-21. doi: 10.1002/ajmg.a.32435. PMID:18629880 doi:10.1002/ajmg.a.32435
  7. ↑ Seemann P, Schwappacher R, Kjaer KW, Krakow D, Lehmann K, Dawson K, Stricker S, Pohl J, Ploger F, Staub E, Nickel J, Sebald W, Knaus P, Mundlos S. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. J Clin Invest. 2005 Sep;115(9):2373-81. Epub 2005 Aug 25. PMID:16127465 doi:10.1172/JCI25118
  8. ↑ Wang X, Xiao F, Yang Q, Liang B, Tang Z, Jiang L, Zhu Q, Chang W, Jiang J, Jiang C, Ren X, Liu JY, Wang QK, Liu M. A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families. Am J Med Genet A. 2006 Sep 1;140A(17):1846-53. PMID:16892395 doi:10.1002/ajmg.a.31372
  9. ↑ Yang W, Cao L, Liu W, Jiang L, Sun M, Zhang D, Wang S, Lo WH, Luo Y, Zhang X. Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. J Hum Genet. 2008;53(4):368-74. Epub 2008 Feb 19. PMID:18283415 doi:10.1007/s10038-008-0253-7
  10. ↑ Dawson K, Seeman P, Sebald E, King L, Edwards M, Williams J 3rd, Mundlos S, Krakow D. GDF5 is a second locus for multiple-synostosis syndrome. Am J Hum Genet. 2006 Apr;78(4):708-12. Epub 2006 Feb 24. PMID:16532400 doi:10.1086/503204
  11. ↑ Seemann P, Schwappacher R, Kjaer KW, Krakow D, Lehmann K, Dawson K, Stricker S, Pohl J, Ploger F, Staub E, Nickel J, Sebald W, Knaus P, Mundlos S. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. J Clin Invest. 2005 Sep;115(9):2373-81. Epub 2005 Aug 25. PMID:16127465 doi:10.1172/JCI25118
  12. ↑ Ploger F, Seemann P, Schmidt-von Kegler M, Lehmann K, Seidel J, Kjaer KW, Pohl J, Mundlos S. Brachydactyly type A2 associated with a defect in proGDF5 processing. Hum Mol Genet. 2008 May 1;17(9):1222-33. doi: 10.1093/hmg/ddn012. Epub 2008 Jan, 18. PMID:18203755 doi:10.1093/hmg/ddn012
  13. ↑ Byrnes AM, Racacho L, Nikkel SM, Xiao F, MacDonald H, Underhill TM, Bulman DE. Mutations in GDF5 presenting as semidominant brachydactyly A1. Hum Mutat. 2010 Oct;31(10):1155-62. doi: 10.1002/humu.21338. PMID:20683927 doi:10.1002/humu.21338
  14. ↑ Bai X, Xiao Z, Pan Y, Hu J, Pohl J, Wen J, Li L. Cartilage-derived morphogenetic protein-1 promotes the differentiation of mesenchymal stem cells into chondrocytes. Biochem Biophys Res Commun. 2004 Dec 10;325(2):453-60. PMID:15530414 doi:10.1016/j.bbrc.2004.10.055
  15. ↑ Kotzsch A, Nickel J, Seher A, Sebald W, Muller TD. Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5-type I receptor specificity. EMBO J. 2009 Apr 8;28(7):937-47. Epub 2009 Feb 19. PMID:19229295 doi:10.1038/emboj.2009.37

3qb4, resolution 2.28Å

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