[PDF][PDF] Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility
J Vaynberg, T Fukuda, K Chen, O Vinogradova… - Molecular cell, 2005 - cell.com
J Vaynberg, T Fukuda, K Chen, O Vinogradova, A Velyvis, Y Tu, L Ng, C Wu, J Qin
Molecular cell, 2005•cell.comWeak protein-protein interactions (PPIs)(KD> 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 KD> 10− 4 M, are poorly explored.
Genome wide, there exist few 3D structures of weak PPIs with KD> 10− 4 M, and none with
KD> 10− 3 M. Here, we report the NMR structure of an extremely weak focal adhesion
complex (KD∼ 3× 10− 3 M) between Nck-2 SH3 domain and PINCH-1 LIM4 domain. The …
biological processes. However, in contrast to a large growing number of well-characterized,
strong PPIs, the weak PPIs, especially those with KD> 10− 4 M, are poorly explored.
Genome wide, there exist few 3D structures of weak PPIs with KD> 10− 4 M, and none with
KD> 10− 3 M. Here, we report the NMR structure of an extremely weak focal adhesion
complex (KD∼ 3× 10− 3 M) between Nck-2 SH3 domain and PINCH-1 LIM4 domain. The …
Abstract
Weak protein-protein interactions (PPIs) (KD > 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 KD > 10−4 M, are poorly explored. Genome wide, there exist few 3D structures of weak PPIs with KD > 10−4 M, and none with KD > 10−3 M. Here, we report the NMR structure of an extremely weak focal adhesion complex (KD∼3 × 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.
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