6VGU

Crystal structure of FERM-folded talin head domain bound to the NPLY motif of beta3-integrin

Summary for 6VGU

• Entry DOI: 10.2210/pdb6vgu/pdb
• Related: 3ivf
• Descriptor: Integrin beta-3,Talin-1 (2 entities in total)
• Functional Keywords: talin, ferm-fold, nply motif, integrin, signaling protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 1
• Total formula weight: 50382.75

Authors

Zhang, P.,Sun, Y.,Wu, J. (deposition date: 2020-01-09, release date: 2020-12-16, Last modification date: 2023-10-11)

Primary citation

Zhang, P.,Azizi, L.,Kukkurainen, S.,Gao, T.,Baikoghli, M.,Jacquier, M.C.,Sun, Y.,Maatta, J.A.E.,Cheng, R.H.,Wehrle-Haller, B.,Hytonen, V.P.,Wu, J.
Crystal structure of the FERM-folded talin head reveals the determinants for integrin binding.
Proc.Natl.Acad.Sci.USA, 117:32402-32412, 2020

PubMed Abstract: Binding of the intracellular adapter proteins talin and its cofactor, kindlin, to the integrin receptors induces integrin activation and clustering. These processes are essential for cell adhesion, migration, and organ development. Although the talin head, the integrin-binding segment in talin, possesses a typical FERM-domain sequence, a truncated form has been crystallized in an unexpected, elongated form. This form, however, lacks a C-terminal fragment and possesses reduced β3-integrin binding. Here, we present a crystal structure of a full-length talin head in complex with the β3-integrin tail. The structure reveals a compact FERM-like conformation and a tightly associated N-P-L-Y motif of β3-integrin. A critical C-terminal poly-lysine motif mediates FERM interdomain contacts and assures the tight association with the β3-integrin cytoplasmic segment. Removal of the poly-lysine motif or disrupting the FERM-folded configuration of the talin head significantly impairs integrin activation and clustering. Therefore, structural characterization of the FERM-folded active talin head provides fundamental understanding of the regulatory mechanism of integrin function.

PubMed: 33288722
DOI: 10.1073/pnas.2014583117

Experimental method

X-RAY DIFFRACTION (2.78 Å)