TY - JOUR
T1 - Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility
AU - Vaynberg, Julia
AU - Fukuda, Tomohiko
AU - Chen, Ka
AU - Vinogradova, Olga
AU - Velyvis, Algirdas
AU - Tu, Yizeng
AU - Ng, Lily
AU - Wu, Chuanyue
AU - Qin, Jun
N1 - Funding Information:
We thank Dr. Tony Pawson (University of Toronto) for providing the Nck1 −/− Nck2 −/− cells; F. Delaglio for nmrPipe software; D. Garrett for Pipp; and Asta Velyviene, Xiaolun Zhang, and Yanwu Yang for technical assistance. The work was supported by National Institutes of Health grants to J.Q. (HL58758, GM62823) and C.W. (DK54639, GM65188).
PY - 2005/2/18
Y1 - 2005/2/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=13944249955&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2004.12.031
DO - 10.1016/j.molcel.2004.12.031
M3 - Article
C2 - 15721255
AN - SCOPUS:13944249955
SN - 1097-2765
VL - 17
SP - 513
EP - 523
JO - Molecular Cell
JF - Molecular Cell
IS - 4
ER -