8k0m: Difference between revisions
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The entry | ==Human collagen prolyl processing enzyme complex, P3H1/CRTAP/PPIB heterotrimer, bound to 2-oxoglutarate== | ||
<StructureSection load='8k0m' size='340' side='right'caption='[[8k0m]], [[Resolution|resolution]] 3.17Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8k0m]] is a 3 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=8K0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8K0M FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.17Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=8k0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8k0m OCA], [https://pdbe.org/8k0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8k0m RCSB], [https://www.ebi.ac.uk/pdbsum/8k0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8k0m ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/P3H1_HUMAN P3H1_HUMAN] Osteogenesis imperfecta type 2;Osteogenesis imperfecta type 3. The disease is caused by variants affecting the gene represented in this entry. A splice site mutation leading to the absence of isoform 1 has been reported in 2 OI8 patients. Isoform 1 is the only form predicted to be located in the endoplasmic reticulum, which the appropriate location for the catalysis of collagen hydroxylation. These patients show indeed severely reduced COL1A1 hydroxylation (PubMed:19088120).<ref>PMID:19088120</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/P3H1_HUMAN P3H1_HUMAN] Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts.<ref>PMID:10951563</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Collagen posttranslational processing is crucial for its proper assembly and function. Disruption of collagen processing leads to tissue development and structure disorders like osteogenesis imperfecta (OI). OI-related collagen processing machinery includes prolyl 3-hydroxylase 1 (P3H1), peptidyl-prolyl cis-trans isomerase B (PPIB), and cartilage-associated protein (CRTAP), with their structural organization and mechanism unclear. We determine cryo-EM structures of the P3H1/CRTAP/PPIB complex. The active sites of P3H1 and PPIB form a face-to-face bifunctional reaction center, indicating a coupled modification mechanism. The structure of the P3H1/CRTAP/PPIB/collagen peptide complex reveals multiple binding sites, suggesting a substrate interacting zone. Unexpectedly, a dual-ternary complex is observed, and the balance between ternary and dual-ternary states can be altered by mutations in the P3H1/PPIB active site and the addition of PPIB inhibitors. These findings provide insights into the structural basis of collagen processing by P3H1/CRTAP/PPIB and the molecular pathology of collagen-related disorders. | |||
The structural basis for the collagen processing by human P3H1/CRTAP/PPIB ternary complex.,Li W, Peng J, Yao D, Rao B, Xia Y, Wang Q, Li S, Cao M, Shen Y, Ma P, Liao R, Qin A, Zhao J, Cao Y Nat Commun. 2024 Sep 8;15(1):7844. doi: 10.1038/s41467-024-52321-6. PMID:39245686<ref>PMID:39245686</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8k0m" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Cao M]] | |||
[[Category: Cao Y]] | |||
[[Category: Li S]] | |||
[[Category: Li W]] | |||
[[Category: Liao R]] | |||
[[Category: Ma P]] | |||
[[Category: Peng J]] | |||
[[Category: Qin A]] | |||
[[Category: Rao B]] | |||
[[Category: Shen Y]] | |||
[[Category: Wang Q]] | |||
[[Category: Xia Y]] | |||
[[Category: Yao D]] | |||
[[Category: Zhao J]] | |||
Latest revision as of 07:50, 18 September 2024
Human collagen prolyl processing enzyme complex, P3H1/CRTAP/PPIB heterotrimer, bound to 2-oxoglutarateHuman collagen prolyl processing enzyme complex, P3H1/CRTAP/PPIB heterotrimer, bound to 2-oxoglutarate
Structural highlights
DiseaseP3H1_HUMAN Osteogenesis imperfecta type 2;Osteogenesis imperfecta type 3. The disease is caused by variants affecting the gene represented in this entry. A splice site mutation leading to the absence of isoform 1 has been reported in 2 OI8 patients. Isoform 1 is the only form predicted to be located in the endoplasmic reticulum, which the appropriate location for the catalysis of collagen hydroxylation. These patients show indeed severely reduced COL1A1 hydroxylation (PubMed:19088120).[1] FunctionP3H1_HUMAN Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts.[2] Publication Abstract from PubMedCollagen posttranslational processing is crucial for its proper assembly and function. Disruption of collagen processing leads to tissue development and structure disorders like osteogenesis imperfecta (OI). OI-related collagen processing machinery includes prolyl 3-hydroxylase 1 (P3H1), peptidyl-prolyl cis-trans isomerase B (PPIB), and cartilage-associated protein (CRTAP), with their structural organization and mechanism unclear. We determine cryo-EM structures of the P3H1/CRTAP/PPIB complex. The active sites of P3H1 and PPIB form a face-to-face bifunctional reaction center, indicating a coupled modification mechanism. The structure of the P3H1/CRTAP/PPIB/collagen peptide complex reveals multiple binding sites, suggesting a substrate interacting zone. Unexpectedly, a dual-ternary complex is observed, and the balance between ternary and dual-ternary states can be altered by mutations in the P3H1/PPIB active site and the addition of PPIB inhibitors. These findings provide insights into the structural basis of collagen processing by P3H1/CRTAP/PPIB and the molecular pathology of collagen-related disorders. The structural basis for the collagen processing by human P3H1/CRTAP/PPIB ternary complex.,Li W, Peng J, Yao D, Rao B, Xia Y, Wang Q, Li S, Cao M, Shen Y, Ma P, Liao R, Qin A, Zhao J, Cao Y Nat Commun. 2024 Sep 8;15(1):7844. doi: 10.1038/s41467-024-52321-6. PMID:39245686[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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