View source for 6gvk


==Second pair of Fibronectin type III domains of integrin beta4 (T1663R mutant) bound to the bullous pemphigoid antigen BP230 (BPAG1e)==
<StructureSection load='6gvk' size='340' side='right'caption='[[6gvk]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gvk]] 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=6GVK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GVK 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]] 1.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6gvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gvk OCA], [https://pdbe.org/6gvk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gvk RCSB], [https://www.ebi.ac.uk/pdbsum/6gvk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gvk 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 ==
Mechanical stability of epithelia requires firm attachment to the basement membrane via hemidesmosomes. Dysfunction of hemidesmosomal proteins causes severe skin-blistering diseases. Two plakins, plectin and BP230 (BPAG1e), link the integrin alpha6beta4 to intermediate filaments in epidermal hemidesmosomes. Here, we show that a linear sequence within the isoform-specific N-terminal region of BP230 binds to the third and fourth FnIII domains of beta4. The crystal structure of the complex and mutagenesis analysis revealed that BP230 binds between the two domains of beta4. BP230 induces closing of the two FnIII domains that are locked in place by an interdomain ionic clasp required for binding. Disruption of BP230-beta4 binding prevents recruitment of BP230 to hemidesmosomes in human keratinocytes, revealing a key role of this interaction for hemidesmosome assembly. Phosphomimetic substitutions in beta4 and BP230 destabilize the complex. Thus, our study provides insights into the architecture of hemidesmosomes and potential mechanisms of regulation.

Integrin alpha6beta4 Recognition of a Linear Motif of Bullous Pemphigoid Antigen BP230 Controls Its Recruitment to Hemidesmosomes.,Manso JA, Gomez-Hernandez M, Carabias A, Alonso-Garcia N, Garcia-Rubio I, Kreft M, Sonnenberg A, de Pereda JM Structure. 2019 Apr 4. pii: S0969-2126(19)30094-2. doi:, 10.1016/j.str.2019.03.016. PMID:31006587<ref>PMID:31006587</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gvk" 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: Gomez-Hernandez M]]
[[Category: Manso JA]]
[[Category: De Pereda JM]]