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- Title
Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling.
- Authors
Velyvis, Algirdas; Vaynberg, Julia; Yang, Yanwu; Vinogradova, Olga; Zhang, Yongjun; Wu, Chuanyue; Qin, Jun
- Abstract
PINCH is an adaptor protein found in focal adhesions, large cellular complexes that link extracellular matrix to the actin cytoskeleton. PINCH, which contains an array of five LIM domains, has been implicated as a platform for multiple protein-protein interactions that mediate integrin signaling within focal adhesions. We had previously characterized the LIM1 domain of PINCH, which functions in focal adhesions by binding specifically to integrin-linked kinase. Using NMR spectroscopy, we show here that the PINCH LIM4 domain, while maintaining the conserved LIM scaffold, recognizes the third SH3 domain of another adaptor protein, Nck2 (also called Nck? or Grb4), in a manner distinct from that of the LIM1 domain. Point mutation of LIM residues in the SH3-binding interface disrupted LIM-SH3 interaction and substantially impaired localization of PINCH to focal adhesions. These data provide novel structural insight into LIM domain-mediated protein-protein recognition and demonstrate that the PINCH-Nck2 interaction is an important component of the focal adhesion assembly during integrin signaling.
- Subjects
PROTEINS; EXTRACELLULAR matrix; CYTOSKELETON; CELL adhesion; INTEGRINS
- Publication
Nature Structural Biology, 2003, Vol 10, Issue 7, p558
- ISSN
1072-8368
- Publication type
Article
- DOI
10.1038/nsb938