PDBsum entry 3osm

Lipid binding protein

PDB id: 3osm

Contents

Protein chain

119 a.a. *

Ligands

SRT

GOL

Waters ×120

* Residue conservation analysis

PDB id:

3osm

Name:

Lipid binding protein

Title:

Structure of the kinase associated domain-1 (ka1) from kcc4p

Structure:

Serine/threonine-protein kinase kcc4. Chain: a. Fragment: kinase associated-1 (ka1) domain, residues 917-1036. Engineered: yes

Source:

Saccharomyces cerevisiae. Brewer's yeast,lager beer yeast,yeast. Organism_taxid: 4932. Gene: kcc4, ycl024w, ycl24w. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.70Å R-factor: 0.188 R-free: 0.197

Authors:

K.Moravcevic,M.A.Lemmon

Key ref:

K.Moravcevic et al. (2010). Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids. Cell, 143, 966-977. PubMed id: 21145462

Date:

09-Sep-10 Release date: 22-Dec-10

Protein chain

P25389  (KCC4_YEAST) -  Probable serine/threonine-protein kinase KCC4 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 1037 a.a.

Struc: 119 a.a.

Enzyme reactions

• Enzyme class: 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

Cell 143:966-977 (2010)

PubMed id: 21145462

Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids.

K.Moravcevic, J.M.Mendrola, K.R.Schmitz, Y.H.Wang, D.Slochower, P.A.Janmey, M.A.Lemmon.

ABSTRACT

Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importance of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to "coincidence detection," allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism.