6U4N

Solution structure of paxillin LIM4 in complex with kindlin-2 F0

Summary for 6U4N

• Entry DOI: 10.2210/pdb6u4n/pdb
• Related: 6U4M
• NMR Information: BMRB: 30659
• Descriptor: Fermitin family homolog 2, Paxillin, ZINC ION (3 entities in total)
• Functional Keywords: lim domain, zinc finger, ubiquitin fold, complex, cell adhesion
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 21442.60

Authors

Zhu, L.,Qin, J. (deposition date: 2019-08-26, release date: 2019-10-23, Last modification date: 2024-05-01)

Primary citation

Zhu, L.,Liu, H.,Lu, F.,Yang, J.,Byzova, T.V.,Qin, J.
Structural Basis of Paxillin Recruitment by Kindlin-2 in Regulating Cell Adhesion.
Structure, 27:1686-, 2019

PubMed Abstract: Activation of cell surface receptor integrin has been extensively studied as the first key step to trigger cell adhesion, but the subsequent events, widely regarded as integrin "outside-in" signaling to form supramolecular complexes (focal adhesions [FAs]) to promote dynamic cell adhesion, remain poorly elucidated. Integrin activator kindlin-2 was recently found to associate with paxillin in nascent FAs, implicating an early yet undefined integrin outside-in signaling event. Here we show structurally that kindlin-2 recognizes paxillin via a distinct interface involving the ubiquitin-like kindlin-2 F0 domain and the paxillin LIM4 domain. The interface is adjacent to the membrane binding site of kindlin-2 F0, suggesting a mechanism for kindlin-2 to recruit paxillin to the membrane-proximal site where FA assembly is initiated. Disruption of the interface impaired the localization of paxillin, causing strong defects in FA assembly and cell migration. These data unveil a structural basis of the kindlin-2/paxillin interaction in controlling dynamic cell adhesion.

PubMed: 31590942
DOI: 10.1016/j.str.2019.09.006

Experimental method

SOLUTION NMR