PDBsum entry 3ixe

Signaling protein/signaling protein

PDB id: 3ixe

Contents

Protein chains

171 a.a. *

70 a.a. *

Metals

_ZN ×2

Waters ×369

* Residue conservation analysis

PDB id:

3ixe

Name:

Signaling protein/signaling protein

Title:

Structural basis of competition between pinch1 and pinch2 for binding to the ankyrin repeat domain of integrin-linked kinase

Structure:

Integrin-linked protein kinase. Chain: a. Fragment: ankyrin repeat domain. Synonym: ilk-1, ilk-2, 59 kda serine/threonine-protein kinase, p59ilk. Engineered: yes. Lim and senescent cell antigen-like-containing domain protein 2. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ilk, ilk1, ilk2. Expressed in: escherichia coli. Expression_system_taxid: 511693. Gene: lims2, pinch2.

Resolution:

1.90Å R-factor: 0.172 R-free: 0.220

Authors:

B.P.Chiswell,A.L.Stiegler,T.J.Boggon,D.A.Calderwood

Key ref:

B.P.Chiswell et al. (2010). Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase. J Struct Biol, 170, 157-163. PubMed id: 19963065

Date:

03-Sep-09 Release date: 15-Dec-09

Protein chain

Q13418  (ILK_HUMAN) -  Scaffold protein ILK from Homo sapiens

Seq: 452 a.a.

Struc: 171 a.a.

Protein chain

Q7Z4I7  (LIMS2_HUMAN) -  LIM and senescent cell antigen-like-containing domain protein 2 from Homo sapiens

Seq: 341 a.a.

Struc: 70 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

J Struct Biol 170:157-163 (2010)

PubMed id: 19963065

Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase.

B.P.Chiswell, A.L.Stiegler, Z.Razinia, E.Nalibotski, T.J.Boggon, D.A.Calderwood.

ABSTRACT

Formation of a heterotrimeric IPP complex composed of integrin-linked kinase (ILK), the LIM domain protein PINCH, and parvin is important for signaling through integrin adhesion receptors. Mammals possess two PINCH genes that are expressed simultaneously in many tissues. PINCH1 and PINCH2 have overlapping functions and can compensate for one another in many settings; however, isoform-specific functions have been reported and it is proposed that association with a PINCH1- or PINCH2-containing IPP complex may provide a bifurcation point in integrin signaling promoting different cellular responses. Here we report that the LIM1 domains of PINCH1 and PINCH2 directly compete for the same binding site on the ankyrin repeat domain (ARD) of ILK. We determined the 1.9A crystal structure of the PINCH2 LIM1 domain complexed with the ARD of ILK, and show that disruption of this interface by point mutagenesis reduces binding in vitro and alters localization of PINCH2 in cells. These studies provide further evidence for the role of the PINCH LIM1 domain in association with ILK and highlight direct competition as one mechanism for regulating which PINCH isoform predominates in IPP complexes. Differential regulation of PINCH1 and PINCH2 expression may therefore provide a means for altering cellular integrin signaling pathways.