PDBsum entry 3gpe

Signaling protein

PDB id: 3gpe

Contents

Protein chain

137 a.a. *

Ligands

PO4

PT5

Metals

_CA ×3

Waters ×92

* Residue conservation analysis

PDB id:

3gpe

Name:

Signaling protein

Title:

Crystal structure analysis of pkc (alpha)-c2 domain complexed with ca2+ and ptdins(4,5)p2

Structure:

Protein kinasE C alpha type. Chain: a. Fragment: c2 domain, unp residues 156-292. Synonym: pkc-alpha, pkc-a. Engineered: yes

Source:

Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Strain: norway rat. Gene: prkca, pkca. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.244 R-free: 0.277

Authors:

C.Ferrer-Orta,J.Querol-Audi,I.Fita,N.Verdaguer

Key ref:

M.Guerrero-Valero et al. (2009). Structural and mechanistic insights into the association of PKCalpha-C2 domain to PtdIns(4,5)P2. Proc Natl Acad Sci U S A, 106, 6603-6607. PubMed id: 19346474 DOI: 10.1073/pnas.0813099106

Date:

23-Mar-09 Release date: 05-May-09

Protein chain

P05696  (KPCA_RAT) -  Protein kinase C alpha type from Rattus norvegicus

Seq: 672 a.a.

Struc: 137 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.13 - protein kinase C.
• 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.0813099106

Proc Natl Acad Sci U S A 106:6603-6607 (2009)

PubMed id: 19346474

Structural and mechanistic insights into the association of PKCalpha-C2 domain to PtdIns(4,5)P2.

M.Guerrero-Valero, C.Ferrer-Orta, J.Querol-Audí, C.Marin-Vicente, I.Fita, J.C.Gómez-Fernández, N.Verdaguer, S.Corbalán-García.

ABSTRACT

C2 domains are widely-spread protein signaling motifs that in classical PKCs act as Ca(2+)-binding modules. However, the molecular mechanisms of their targeting process at the plasma membrane remain poorly understood. Here, the crystal structure of PKCalpha-C2 domain in complex with Ca(2+), 1,2-dihexanoyl-sn-glycero-3-[phospho-L-serine] (PtdSer), and 1,2-diayl-sn-glycero-3-[phosphoinositol-4,5-bisphosphate] [PtdIns(4,5)P(2)] shows that PtdSer binds specifically to the calcium-binding region, whereas PtdIns(4,5)P(2) occupies the concave surface of strands beta3 and beta4. Strikingly, the structure reveals a PtdIns(4,5)P(2)-C2 domain-binding mode in which the aromatic residues Tyr-195 and Trp-245 establish direct interactions with the phosphate moieties of the inositol ring. Mutations that abrogate Tyr-195 and Trp-245 recognition of PtdIns(4,5)P(2) severely impaired the ability of PKCalpha to localize to the plasma membrane. Notably, these residues are highly conserved among C2 domains of topology I, and a general mechanism of C2 domain-membrane docking mediated by PtdIns(4,5)P(2) is presented.

Selected figure(s)

Figure 1.
Structure of PKCα C2 domain bound to PtdIns(4,5)P[2]. (A) The PKCαC2-Ca^2+-PtdIns(4,5)P[2] ternary complex. (B) The PKCαC2-Ca^2+-PS-PtdIns(4,5)P[2] quaternary complex. The C2 molecule is shown in blue. The calcium ions located at the tip of the domain in the calcium-binding regions are represented as green spheres. The phosphate ion and the phospholipids molecules are depicted as sticks. (C) View of the β3–β4 groove, showing the interactions between the C2 domain and the IP[3] headgroup of PtdIns(4,5)P[2]. The C2 residues are represented as blue sticks and explicitly labeled. The InsP[3] molecule is shown in sticks in atom type code. Hydrogen bonds are shown as dashed lines in black. An omit |F[o]| − |F[c]| electron density map, contoured at 3.0 σ, is shown in green around the InsP[3] molecule.

Figure 4.
Docking of the PKCα-C2 domain into the membrane surface. (A) The model membrane corresponds to a POPC molecular dynamics simulation with coordinates (Protein Data Bank ID code popc128a). Half of the membrane bilayer is represented (thin sticks). The C2 domain in represented as its potential surface as computed by GRASP (33) and displayed by PyMol (www.pymol.org). Ca^2+ ions are shown as green spheres. The head groups of the 2 interacting phospholipids, PtdSer and PtdIns(4,5)P[2] (thick sticks), served as reference for the docking model. (B) Close-up of the PtdSer and PtdIns(4,5)P[2] interacting surfaces.

Figures were selected by an automated process.