PDBsum entry 3kmw

Cell adhesion

PDB id: 3kmw

Contents

Protein chains

268 a.a. *

124 a.a. *

Ligands

ATP

Metals

_MG

Waters ×309

* Residue conservation analysis

PDB id:

3kmw

Name:

Cell adhesion

Title:

Crystal structure of the ilk/alpha-parvin core complex (mgatp)

Structure:

Integrin-linked kinase. Chain: a. Fragment: c-terminal pseudokinase domain: unp residues 183-452. Synonym: ilk. Engineered: yes. Mutation: yes. Alpha-parvin. Chain: b. Fragment: c-terminal calponin homology domain: unp residues 248-372.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ilk, ilk1, ilk2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: parva, mxra2.

Resolution:

2.00Å R-factor: 0.199 R-free: 0.203

Authors:

K.Fukuda,J.Qin

Key ref:

K.Fukuda et al. (2009). The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to focal adhesions. Mol Cell, 36, 819-830. PubMed id: 20005845 DOI: 10.1016/j.molcel.2009.11.028

Date:

11-Nov-09 Release date: 29-Dec-09

Protein chain

Q13418  (ILK_HUMAN) -  Scaffold protein ILK from Homo sapiens

Seq: 452 a.a.

Struc: 268 a.a.*

Protein chain

Q9NVD7  (PARVA_HUMAN) -  Alpha-parvin from Homo sapiens

Seq: 372 a.a.

Struc: 124 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.molcel.2009.11.028

Mol Cell 36:819-830 (2009)

PubMed id: 20005845

The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to focal adhesions.

K.Fukuda, S.Gupta, K.Chen, C.Wu, J.Qin.

ABSTRACT

Integrin-linked kinase (ILK) plays a pivotal role in connecting transmembrane receptor integrin to the actin cytoskeleton and thereby regulating diverse cell-adhesion-dependent processes. The kinase domain (KD) of ILK is indispensable for its function, but the underlying molecular basis remains enigmatic. Here we present the crystal structure of the ILK KD bound to its cytoskeletal regulator, the C-terminal calponin homology domain of alpha-parvin. While maintaining a canonical kinase fold, the ILK KD displays a striking pseudoactive site conformation. We show that rather than performing the kinase function, this conformation specifically recognizes alpha-parvin for promoting effective assembly of ILK into focal adhesions. The alpha-parvin-bound ILK KD can simultaneously engage integrin beta cytoplasmic tails. These results thus define ILK as a distinct pseudokinase that mechanically couples integrin and alpha-parvin for mediating cell adhesion. They also highlight functional diversity of the kinase fold and its "active" site in mediating many biological processes.

Selected figure(s)

Figure 2.
Figure 2. Structural Comparison of the Activation Segment
(A) An orthogonal view of the activation segment. (Left) The activation segment (green) in ILK KD. The side chains of S343 and E238 (αC helix) are depicted in stick models. (Right) The activation segment (yellow) in PKA.
(B) Divergent activation segment in the ILK KD structure. (Left) Overall tube model of the ILK KD and the location of the activation segment that can interact with a cluster of hydrophobic residues in the N-lobe. (Right) A detailed view of hydrophobic and polar interactions formed between the activation segment and the N-lobe (<4 Å). See also Figure S2.

Figure 7.
Figure 7. Hydrophobic Spine Motifs in Active Kinases and ILK
(A) Overall structure of the ILK KD and location of the hydrophobic spine motifs. The hydrophobic residues in the regulatory (R) and catalytic (C) spines are depicted in stick models rendered in the transparent surfaces colored in green and blue, respectively. The conserved αF helix and the aspartate residue D374 are highlighted.
(B) Close-up view of the R- and C-spine motifs in the ILK KD apo form.
(C) Close-up view of the R- and C-spine motifs in the ILK KD bound to Mg and ATP. ATP has no effect on the spines.
(D) Close-up view of the R- and C-spine motifs in inactive protein kinase CDK2 (PDB ID 1HCL) (apo form).
(E) Close-up view of the R- and C-spine motifs in the active CDK2 (PDB ID 1FIN) bound to ATP. Note that the R-spine motif is disrupted in (D), as compared to those in ILK KD in (C) and active CDK2 in (E).
(F) Overlay of the R- and C-spine motifs, and other key segments between the ATP-bound ILK KD and the active CDK2, showing a similar spine formation between ILK and active CDK2 kinase. See also Figure S7.

The above figures are reprinted by permission from Cell Press: Mol Cell (2009, 36, 819-830) copyright 2009.

Figures were selected by an automated process.