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Structural basis of adhesion‐molecule recognition by ERM proteins revealed by the crystal structure of the radixin—ICAM‐2 complex
Author(s) -
Hamada Keisuke,
Shimizu Toshiyuki,
Yonemura Shigenobu,
Tsukita Shoichiro,
Tsukita Sachiko,
Hakoshima Toshio
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg039
Subject(s) - radixin , moesin , ezrin , biology , phosphotyrosine binding domain , ferm domain , peptide sequence , peptide , microbiology and biotechnology , plasma protein binding , protein structure , biochemistry , biophysics , cytoskeleton , membrane protein , integral membrane protein , signal transduction , membrane , gene , sh2 domain , cell , receptor tyrosine kinase
ERM (ezrin/radixin/moesin) proteins recognize the cytoplasmic domains of adhesion molecules in the formation of the membrane‐associated cytoskeleton. Here we report the crystal structure of the radixin FERM (4.1 and ERM) domain complexed with the ICAM‐2 cytoplasmic peptide. The non‐polar region of the ICAM‐2 peptide contains the RxxTYxVxxA sequence motif to form a β‐strand followed by a short 3 10 ‐helix. It binds the groove of the phosphotyrosine‐binding (PTB)‐like subdomain C mediated by a β—β association and several side‐chain interactions. The binding mode of the ICAM‐2 peptide to the FERM domain is distinct from that of the NPxY motif‐containing peptide binding to the canonical PTB domain. Mutation analyses based on the crystal structure reveal the determinant elements of recognition and provide the first insights into the physical link between adhesion molecules and ERM proteins.