1NYP

4th LIM domain of PINCH protein

Summary for 1NYP

• Entry DOI: 10.2210/pdb1nyp/pdb
• Related: 1g47
• Descriptor: PINCH protein, ZINC ION (2 entities in total)
• Functional Keywords: lim domain, protein recognition, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Cell junction, focal adhesion: P48059
• Total number of polymer chains: 1
• Total formula weight: 7663.56

Authors

Velyvis, A.,Vaynberg, J.,Vinogradova, O.,Zhang, Y.,Wu, C.,Qin, J. (deposition date: 2003-02-13, release date: 2003-07-01, Last modification date: 2024-05-22)

Primary citation

Velyvis, A.,Vaynberg, J.,Yang, Y.,Vinogradova, O.,Zhang, Y.,Wu, C.,Qin, J.
Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling
Nat.Struct.Biol., 10:558-564, 2003

PubMed 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 Nckbeta 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.

PubMed: 12794636
DOI: 10.1038/nsb938

Experimental method

SOLUTION NMR