View source for 5dcp


==Crystal structure of the human filamin B Ig-like domains 16-17==
<StructureSection load='5dcp' size='340' side='right'caption='[[5dcp]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5dcp]] is a 2 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=5DCP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DCP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.49&#8491;</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=5dcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dcp OCA], [https://pdbe.org/5dcp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dcp RCSB], [https://www.ebi.ac.uk/pdbsum/5dcp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dcp ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FLNB_HUMAN FLNB_HUMAN] Note=Interaction with FLNA may compensate for dysfunctional FLNA homodimer in the periventricular nodular heterotopia (PVNH) disorder.  Defects in FLNB are the cause of atelosteogenesis type 1 (AO1) [MIM:[https://omim.org/entry/108720 108720]; also known as giant cell chondrodysplasia or spondylohumerofemoral hypoplasia. Atelosteogenesis are lethal short-limb skeletal dysplasias with vertebral abnormalities, disharmonious skeletal maturation, poorly modeled long bones and joint dislocations.<ref>PMID:14991055</ref>   Defects in FLNB are the cause of atelosteogenesis type 3 (AO3) [MIM:[https://omim.org/entry/108721 108721]. Atelosteogenesis are short-limb lethal skeletal dysplasias with vertebral abnormalities, disharmonious skeletal maturation, poorly modeled long bones and joint dislocations. In AO3 recurrent respiratory insufficiency and/or infections usually result in early death.<ref>PMID:14991055</ref>   Defects in FLNB are the cause of boomerang dysplasia (BOOMD) [MIM:[https://omim.org/entry/112310 112310]. This is a perinatal lethal osteochondrodysplasia characterized by absence or underossification of the limb bones and vertebre. Boomerang dysplasia is distinguished from atelosteogenesis on the basis of a more severe defect in mineralisation, with complete absence of ossification in some limb elements and vertebral segments.<ref>PMID:15994868</ref>   Defects in FLNB are the cause of Larsen syndrome (LRS) [MIM:[https://omim.org/entry/150250 150250]. An osteochondrodysplasia characterized by large-joint dislocations and characteristic craniofacial abnormalities. The cardinal features of the condition are dislocations of the hip, knee and elbow joints, with equinovarus or equinovalgus foot deformities. Spatula-shaped fingers, most marked in the thumb, are also present. Craniofacial anomalies include hypertelorism, prominence of the forehead, a depressed nasal bridge, and a flattened midface. Cleft palate and short stature are often associated features. Spinal anomalies include scoliosis and cervical kyphosis. Hearing loss is a well-recognized complication.<ref>PMID:14991055</ref> <ref>PMID:16801345</ref>   Defects in FLNB are the cause of spondylocarpotarsal synostosis syndrome (SCT) [MIM:[https://omim.org/entry/272460 272460]; also known as spondylocarpotarsal syndrome (SCT) or congenital synspondylism or vertebral fusion with carpal coalition or congenital scoliosis with unilateral unsegmented bar. The disorder is characterized by short stature and vertebral, carpal and tarsal fusions.<ref>PMID:14991055</ref> 
== Function ==
[https://www.uniprot.org/uniprot/FLNB_HUMAN FLNB_HUMAN] Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cells' ability to sense mechanical cues in their environment is crucial for fundamental cellular processes, leading defects in mechanosensing to be linked to many diseases. The actin cross-linking protein Filamin has an important role in the conversion of mechanical forces into biochemical signals. Here, we reveal how mutations in Filamin genes known to cause Larsen syndrome and Frontometaphyseal dysplasia can affect the structure and therefore function of Filamin domains 16 and 17. Employing X-ray crystallography, the structure of these domains was first solved for the human Filamin B. The interaction seen between domains 16 and 17 is broken by shear force as revealed by steered molecular dynamics simulations. The effects of skeletal dysplasia associated mutations of the structure and mechanosensing properties of Filamin were studied by combining various experimental and theoretical techniques. The results showed that Larsen syndrome associated mutations destabilize or even unfold domain 17. Interestingly, those Filamin functions that are mediated via domain 17 interactions with other proteins are not necessarily affected as strongly interacting peptide binding to mutated domain 17 induces at least partial domain folding. Mutation associated to Frontometaphyseal dysplasia, in turn, transforms 16-17 fragment from compact to an elongated form destroying the force-regulated domain pair.

Skeletal Dysplasia Mutations Effect on Human Filamins' Structure and Mechanosensing.,Seppala J, Bernardi RC, Haataja TJK, Hellman M, Pentikainen OT, Schulten K, Permi P, Ylanne J, Pentikainen U Sci Rep. 2017 Jun 26;7(1):4218. doi: 10.1038/s41598-017-04441-x. PMID:28652603<ref>PMID:28652603</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5dcp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Filamin 3D structures|Filamin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Pentikainen U]]
[[Category: Seppala J]]
[[Category: Ylanne J]]