1U5S

NMR structure of the complex between Nck-2 SH3 domain and PINCH-1 LIM4 domain

Summary for 1U5S

• Entry DOI: 10.2210/pdb1u5s/pdb
• Descriptor: Cytoplasmic protein NCK2, PINCH protein, ZINC ION (3 entities in total)
• Functional Keywords: protein-protein complex, beta barrel, beta sheet, zinc finger, metal binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: O43639; Cell junction, focal adhesion: P48059
• Total number of polymer chains: 2
• Total formula weight: 15726.63

Authors

Vaynberg, J.,Fukuda, T.,Vinogradova, O.,Velyvis, A.,Ng, L.,Wu, C.,Qin, J. (deposition date: 2004-07-28, release date: 2005-04-05, Last modification date: 2024-05-22)

Primary citation

Vaynberg, J.,Fukuda, T.,Chen, K.,Vinogradova, O.,Velyvis, A.,Tu, Y.,Ng, L.,Wu, C.,Qin, J.
Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility.
Mol.Cell, 17:513-523, 2005

PubMed Abstract: Weak protein-protein interactions (PPIs) (K(D) > 10(-6) M) are critical determinants of many biological processes. However, in contrast to a large growing number of well-characterized, strong PPIs, the weak PPIs, especially those with K(D) > 10(-4) M, are poorly explored. Genome wide, there exist few 3D structures of weak PPIs with K(D) > 10(-4) M, and none with K(D) > 10(-3) M. Here, we report the NMR structure of an extremely weak focal adhesion complex (K(D) approximately 3 x 10(-3) M) between Nck-2 SH3 domain and PINCH-1 LIM4 domain. The structure exhibits a remarkably small and polar interface with distinct binding modes for both SH3 and LIM domains. Such an interface suggests a transient Nck-2/PINCH-1 association process that may trigger rapid focal adhesion turnover during integrin signaling. Genetic rescue experiments demonstrate that this interface is indeed involved in mediating cell shape change and migration. Together, the data provide a molecular basis for an ultraweak PPI in regulating focal adhesion dynamics during integrin signaling.

PubMed: 15721255
DOI: 10.1016/j.molcel.2004.12.031

Experimental method

SOLUTION NMR