Document Detail


Structural basis of the interaction between integrin alpha6beta4 and plectin at the hemidesmosomes.
MedLine Citation:
PMID:  19242489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The interaction between the integrin alpha6beta4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane. We describe the crystal structure at 2.75 A resolution of the primary alpha6beta4-plectin complex, formed by the first pair of fibronectin type III domains and the N-terminal region of the connecting segment of beta4 and the actin-binding domain of plectin. Two missense mutations in beta4 (R1225H and R1281W) linked to nonlethal forms of epidermolysis bullosa prevent essential intermolecular contacts. We also present two structures at 1.75 and 2.05 A resolution of the beta4 moiety in the absence of plectin, which reveal a major rearrangement of the connecting segment of beta4 on binding to plectin. This conformational switch is correlated with the way alpha6beta4 promotes stable adhesion or cell migration and suggests an allosteric control of the integrin.
Authors:
José M de Pereda; M Pilar Lillo; Arnoud Sonnenberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-26
Journal Detail:
Title:  The EMBO journal     Volume:  28     ISSN:  1460-2075     ISO Abbreviation:  EMBO J.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-22     Completed Date:  2009-05-04     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  1180-90     Citation Subset:  IM    
Affiliation:
Department of Structural Biology, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Campus Unamuno, Salamanca, Spain. pereda@usal.es
Data Bank Information
Bank Name/Acc. No.:
PDB/3F7P;  3F7Q;  3F7R
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Crystallography, X-Ray
Epidermolysis Bullosa / genetics,  metabolism
Hemidesmosomes / metabolism*,  ultrastructure
Integrin alpha6beta4 / chemistry*,  genetics,  metabolism*
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes / metabolism
Mutation, Missense
Plectin / chemistry*,  genetics,  metabolism*
Protein Binding
Protein Conformation*
Chemical
Reg. No./Substance:
0/Integrin alpha6beta4; 0/Multiprotein Complexes; 0/Plectin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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