PDBsum entry 4f7g

Cell adhesion

PDB id: 4f7g

Contents

Protein chains

192 a.a.

170 a.a.

Waters ×109

PDB id:

4f7g

Name:

Cell adhesion

Title:

Crystal structure of talin autoinhibition complex

Structure:

Talin-1. Chain: a. Fragment: f2f3 subdomain, unp residues 206-405. Engineered: yes. Talin-1. Chain: b. Fragment: rs subdomain, unp residues 1654-1847. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: tln1, tln. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Resolution:

2.05Å R-factor: 0.212 R-free: 0.249

Authors:

X.Song,J.Qin,S.Ye,R.Zhang

Key ref:

X.Song et al. (2012). A novel membrane-dependent on/off switch mechanism of talin FERM domain at sites of cell adhesion. Cell Res, 22, 1533-1545. PubMed id: 22710802

Date:

16-May-12 Release date: 04-Jul-12

Protein chain

P26039  (TLN1_MOUSE) -  Talin-1 from Mus musculus

Seq: 2541 a.a.

Struc: 192 a.a.

Protein chain

P26039  (TLN1_MOUSE) -  Talin-1 from Mus musculus

Seq: 2541 a.a.

Struc: 170 a.a.

Cell Res 22:1533-1545 (2012)

PubMed id: 22710802

A novel membrane-dependent on/off switch mechanism of talin FERM domain at sites of cell adhesion.

X.Song, J.Yang, J.Hirbawi, S.Ye, H.D.Perera, E.Goksoy, P.Dwivedi, E.F.Plow, R.Zhang, J.Qin.

ABSTRACT

The activation of heterodimeric (α/β) integrin transmembrane receptors by cytosolic protein talin is crucial for regulating diverse cell-adhesion-dependent processes, including blood coagulation, tissue remodeling, and cancer metastasis. This process is triggered by the coincident binding of N-terminal FERM (four-point-one-protein/ezrin/radixin/moesin) domain of talin (talin-FERM) to the inner membrane surface and integrin β cytoplasmic tail, but how these binding events are spatiotemporally regulated remains obscure. Here we report the crystal structure of a dormant talin, revealing how a C-terminal talin rod segment (talin-RS) self-masks a key integrin-binding site on talin-FERM via a large interface. Unexpectedly, the structure also reveals a distinct negatively charged surface on talin-RS that electrostatically hinders the talin-FERM binding to the membrane. Such a dual inhibitory topology for talin is consistent with the biochemical and functional data, but differs significantly from a previous model. We show that upon enrichment with phosphotidylinositol-4,5-bisphosphate (PIP2) - a known talin activator, membrane strongly attracts a positively charged surface on talin-FERM and simultaneously repels the negatively charged surface on talin-RS. Such an electrostatic "pull-push" process promotes the relief of the dual inhibition of talin-FERM, which differs from the classic "steric clash" model for conventional PIP2-induced FERM domain activation. These data therefore unravel a new type of membrane-dependent FERM domain regulation and illustrate how it mediates the talin on/off switches to regulate integrin transmembrane signaling and cell adhesion.