PDBsum entry 3f6q

Signaling protein/signaling protein

PDB id: 3f6q

Contents

Protein chains

169 a.a. *

72 a.a. *

Ligands

PO4

Metals

IOD ×18

_ZN ×2

Waters ×363

* Residue conservation analysis

PDB id:

3f6q

Name:

Signaling protein/signaling protein

Title:

Crystal structure of integrin-linked kinase ankyrin repeat domain in complex with pinch1 lim1 domain

Structure:

Integrin-linked protein kinase. Chain: a. Fragment: unp residues 1-170, 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 1. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ilk, ilk1, ilk2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: lims1, pinch, pinch1.

Resolution:

1.60Å R-factor: 0.163 R-free: 0.199

Authors:

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

Key ref:

B.P.Chiswell et al. (2008). The structural basis of integrin-linked kinase-PINCH interactions. Proc Natl Acad Sci U S A, 105, 20677-20682. PubMed id: 19074270 DOI: 10.1073/pnas.0811415106

Date:

06-Nov-08 Release date: 02-Dec-08

Protein chain

Q13418  (ILK_HUMAN) -  Scaffold protein ILK from Homo sapiens

Seq: 452 a.a.

Struc: 169 a.a.

Protein chain

P48059  (LIMS1_HUMAN) -  LIM and senescent cell antigen-like-containing domain protein 1 from Homo sapiens

Seq: 325 a.a.

Struc: 72 a.a.*

* PDB and UniProt seqs differ at 5 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

DOI no: 10.1073/pnas.0811415106

Proc Natl Acad Sci U S A 105:20677-20682 (2008)

PubMed id: 19074270

The structural basis of integrin-linked kinase-PINCH interactions.

B.P.Chiswell, R.Zhang, J.W.Murphy, T.J.Boggon, D.A.Calderwood.

ABSTRACT

The heterotrimeric complex between integrin-linked kinase (ILK), PINCH, and parvin is an essential signaling platform, serving as a convergence point for integrin and growth-factor signaling and regulating cell adhesion, spreading, and migration. We report a 1.6-A crystal structure of the ILK ankyrin repeat domain bound to the PINCH1 LIM1 domain, revealing the molecular basis of ILK-PINCH interactions and providing a structural description of this region of ILK. This structure identifies 5 ankyrin repeats in ILK, explains previous deletion mutagenesis data, permits identification of ILK and PINCH1 point mutations that disrupt the interaction, shows how zincs are coordinated by PINCH1 LIM1, and suggests that conformational flexibility and twisting between the 2 zinc fingers within the LIM1 domain may be important for ILK binding. These data provide an atomic-resolution description of a key interaction in the ILK-PINCH-parvin scaffolding complex.

Selected figure(s)

Figure 1.
Structure of the ILK ANK repeat domain in complex with PINCH LIM1. (A) Schematic showing the domains of ILK and PINCH. (B) Cartoon of the structure of the LIM1 domain of PINCH1 in complex with ILK. PINCH1 is shown in light green with zincs as yellow spheres and the vector-derived N-terminal β-strand (strand −z) in light blue. ILK is colored according to ANK repeat (ANK1 yellow; ANK2 red; ANK3 green; ANK4 purple; ANK5 blue). This color scheme is maintained throughout the manuscript. (C) Example 2F[o]-F[c] electron density maps contoured at 1.5 σ. Clear density for ILK residues Tyr-106 and Trp-110 is visible. All figures are made by using PYMOL (www.pymol.org).

Figure 4.
Architecture of the interaction. (Center) Illustration of a top-view schematic of the ILK interaction with PINCH1. Three views show this interaction from different angles. (Left) Toward PINCH1 (gray surface) from the ILK ANK repeat finger side of the interaction. Lower images are toward PINCH1 (gray surface) from the ILK ANK repeat palm side of the interaction. (Right) Toward ILK (gray surface). Shown in red is PINCH1 backbone trace. Blown-up views show labels for residues involved in the interaction.

Figures were selected by an automated process.