PDBsum entry 4edm

Signaling protein

PDB id: 4edm

Contents

Protein chain

127 a.a.

Ligands

EDO ×7

Waters ×116

PDB id:

4edm

Name:

Signaling protein

Title:

Crystal structure of beta-parvin ch2 domain

Structure:

Beta-parvin. Chain: a, b. Fragment: c-terminal calponin homology domain. Synonym: affixin. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: parvb, cgi-56. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.00Å R-factor: 0.214 R-free: 0.253

Authors:

A.L.Stiegler,K.M.Draheim,X.Li,N.E.Chayen,D.A.Calderwood,T.J.Boggon

Key ref:

A.L.Stiegler et al. (2012). Structural basis for paxillin binding and focal adhesion targeting of β-parvin. J Biol Chem, 287, 32566-32577. PubMed id: 22869380 DOI: 10.1074/jbc.M112.367342

Date:

27-Mar-12 Release date: 08-Aug-12

Protein chains

Q9HBI1  (PARVB_HUMAN) -  Beta-parvin from Homo sapiens

Seq: 364 a.a.

Struc: 127 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M112.367342

J Biol Chem 287:32566-32577 (2012)

PubMed id: 22869380

Structural basis for paxillin binding and focal adhesion targeting of β-parvin.

A.L.Stiegler, K.M.Draheim, X.Li, N.E.Chayen, D.A.Calderwood, T.J.Boggon.

ABSTRACT

β-Parvin is a cytoplasmic adaptor protein that localizes to focal adhesions where it interacts with integrin-linked kinase and is involved in linking integrin receptors to the cytoskeleton. It has been reported that despite high sequence similarity to α-parvin, β-parvin does not bind paxillin, suggesting distinct interactions and cellular functions for these two closely related parvins. Here, we reveal that β-parvin binds directly and specifically to leucine-aspartic acid repeat (LD) motifs in paxillin via its C-terminal calponin homology (CH2) domain. We present the co-crystal structure of β-parvin CH2 domain in complex with paxillin LD1 motif to 2.9 Å resolution and find that the interaction is similar to that previously observed between α-parvin and paxillin LD1. We also present crystal structures of unbound β-parvin CH2 domain at 2.1 Å and 2.0 Å resolution that show significant conformational flexibility in the N-terminal α-helix, suggesting an induced fit upon paxillin binding. We find that β-parvin has specificity for the LD1, LD2, and LD4 motifs of paxillin, with K(D) values determined to 27, 42, and 73 μm, respectively, by surface plasmon resonance. Furthermore, we show that proper localization of β-parvin to focal adhesions requires both the paxillin and integrin-linked kinase binding sites and that paxillin is important for early targeting of β-parvin. These studies provide the first molecular details of β-parvin binding to paxillin and help define the requirements for β-parvin localization to focal adhesions.