7C3M

Structure of FERM protein

Summary for 7C3M

• Entry DOI: 10.2210/pdb7c3m/pdb
• Descriptor: Fermitin family homolog 3,Fermitin family homolog 3,Fermitin family homolog 3 (1 entity in total)
• Functional Keywords: ferm protein, kindlin, integrin, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 229388.25

Authors

Bu, W.,Loh, Z.Y.,Jin, S.,Basu, S.,Ero, R.,Park, J.E.,Yan, X.,Wang, M.,Sze, S.K.,Tan, S.M.,Gao, Y.G. (deposition date: 2020-05-13, release date: 2020-06-03, Last modification date: 2024-03-27)

Primary citation

Bu, W.,Levitskaya, Z.,Loh, Z.Y.,Jin, S.,Basu, S.,Ero, R.,Yan, X.,Wang, M.,Ngan, S.F.C.,Sze, S.K.,Tan, S.M.,Gao, Y.G.
Structural basis of human full-length kindlin-3 homotrimer in an auto-inhibited state.
Plos Biol., 18:e3000755-e3000755, 2020

PubMed Abstract: Kindlin-1, -2, and -3 directly bind integrin β cytoplasmic tails to regulate integrin activation and signaling. Despite their functional significance and links to several diseases, structural information on full-length kindlin proteins remains unknown. Here, we report the crystal structure of human full-length kindlin-3, which reveals a novel homotrimer state. Unlike kindlin-3 monomer, which is the major population in insect and mammalian cell expression systems, kindlin-3 trimer does not bind integrin β cytoplasmic tail as the integrin-binding pocket in the F3 subdomain of 1 protomer is occluded by the pleckstrin homology (PH) domain of another protomer, suggesting that kindlin-3 is auto-inhibited upon trimer formation. This is also supported by functional assays in which kindlin-3 knockout K562 erythroleukemia cells reconstituted with the mutant kindlin-3 containing trimer-disrupting mutations exhibited an increase in integrin-mediated adhesion and spreading on fibronectin compared with those reconstituted with wild-type kindlin-3. Taken together, our findings reveal a novel mechanism of kindlin auto-inhibition that involves its homotrimer formation.

PubMed: 32644996
DOI: 10.1371/journal.pbio.3000755

Experimental method

X-RAY DIFFRACTION (3.6 Å)