View source for 4wtx


==Crystal structure of the fourth FnIII domain of integrin beta4==
<StructureSection load='4wtx' size='340' side='right'caption='[[4wtx]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wtx]] is a 1 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=4WTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WTX 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]] 1.5&#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=4wtx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtx OCA], [https://pdbe.org/4wtx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wtx RCSB], [https://www.ebi.ac.uk/pdbsum/4wtx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtx ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ITB4_HUMAN ITB4_HUMAN] Defects in ITGB4 are a cause of epidermolysis bullosa letalis with pyloric atresia (EB-PA) [MIM:[https://omim.org/entry/226730 226730]; also known as junctional epidermolysis bullosa with pyloric atresia (PA-JEB) or aplasia cutis congenita with gastrointestinal atresia. EB-PA is an autosomal recessive, frequently lethal, epidermolysis bullosa with variable involvement of skin, nails, mucosa, and with variable effects on the digestive system. It is characterized by mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal atresia, which most commonly affects the pylorus. Pyloric atresia is a primary manifestation rather than a scarring process secondary to epidermolysis bullosa.<ref>PMID:9792864</ref> <ref>PMID:9422533</ref> <ref>PMID:9546354</ref> <ref>PMID:9892956</ref> <ref>PMID:10873890</ref> <ref>PMID:11251584</ref> <ref>PMID:11328943</ref>   Defects in ITGB4 are a cause of generalized atrophic benign epidermolysis bullosa (GABEB) [MIM:[https://omim.org/entry/226650 226650]. GABEB is a non-lethal, adult form of junctional epidermolysis bullosa characterized by life-long blistering of the skin, associated with hair and tooth abnormalities.<ref>PMID:10792571</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ITB4_HUMAN ITB4_HUMAN] Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility.<ref>PMID:12482924</ref> <ref>PMID:19403692</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Integrin alpha6beta4 is a major component of hemidesmosomes that mediate the stable anchorage of epithelial cells to the underlying basement membrane. Integrin alpha6beta4 has also been implicated in cell proliferation and migration and in carcinoma progression. The third and fourth fibronectin type III domains (FnIII-3,4) of integrin beta4 mediate binding to the hemidesmosomal proteins BPAG1e and BPAG2, and participate in signalling. Here, it is demonstrated that X-ray crystallography, small-angle X-ray scattering and double electron-electron resonance (DEER) complement each other to solve the structure of the FnIII-3,4 region. The crystal structures of the individual FnIII-3 and FnIII-4 domains were solved and the relative arrangement of the FnIII domains was elucidated by combining DEER with site-directed spin labelling. Multiple structures of the interdomain linker were modelled by Monte Carlo methods complying with DEER constraints, and the final structures were selected against experimental scattering data. FnIII-3,4 has a compact and cambered flat structure with an evolutionary conserved surface that is likely to correspond to a protein-interaction site. Finally, this hybrid method is of general application for the study of other macromolecules and complexes.

Combination of X-ray crystallography, SAXS and DEER to obtain the structure of the FnIII-3,4 domains of integrin alpha6beta4.,Alonso-Garcia N, Garcia-Rubio I, Manso JA, Buey RM, Urien H, Sonnenberg A, Jeschke G, de Pereda JM Acta Crystallogr D Biol Crystallogr. 2015 Apr;71(Pt 4):969-85. doi:, 10.1107/S1399004715002485. Epub 2015 Mar 27. PMID:25849406<ref>PMID:25849406</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wtx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Integrin 3D structures|Integrin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alonso-Garcia N]]
[[Category: Buey RM]]
[[Category: Urien H]]
[[Category: De Pereda JM]]