PDBsum entry 3pcs

Protein transport/transferase

PDB id: 3pcs

Contents

Protein chains

350 a.a.

14 a.a.

12 a.a.

13 a.a.

Ligands

VAL-LEU-ASP-VAL-LEU-LYS-PHE-TYR-ASP-SER

PDB id:

3pcs

Name:

Protein transport/transferase

Title:

Structure of espg-pak2 autoinhibitory ialpha3 helix complex

Structure:

Espg. Chain: a, b, c, d. Synonym: espg protein. Engineered: yes. Serine/threonine-protein kinase pak 2. Chain: e, f, g, h. Fragment: unp residues 121-136. Synonym: gamma-pak, pak65, s6/h4 kinase, p21-activated kinase 2, pak- 2, p58, pak-2p27, p27, pak-2p34, p34, c-t-pak2.

Source:

Escherichia coli. Organism_taxid: 83334. Strain: o157:h7. Gene: ecs4590, espg, z5142. Expressed in: escherichia coli. Expression_system_taxid: 469008. Homo sapiens. Human. Organism_taxid: 9606.

Resolution:

2.86Å R-factor: 0.195 R-free: 0.281

Authors:

D.R.Tomchick,N.M.Alto,A.S.Selyunin

Key ref:

A.S.Selyunin et al. (2011). The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold. Nature, 469, 107-111. PubMed id: 21170023

Date:

21-Oct-10 Release date: 05-Jan-11

Protein chains

Q7DB50  (Q7DB50_ECO57) -  T3SS secreted effector EspG from Escherichia coli O157:H7

Seq: 381 a.a.

Struc: 350 a.a.

Protein chain

Q13177  (PAK2_HUMAN) -  Serine/threonine-protein kinase PAK 2 from Homo sapiens

Seq: 524 a.a.

Struc: 14 a.a.

Protein chain

Q13177  (PAK2_HUMAN) -  Serine/threonine-protein kinase PAK 2 from Homo sapiens

Seq: 524 a.a.

Struc: 12 a.a.

Protein chain

Q13177  (PAK2_HUMAN) -  Serine/threonine-protein kinase PAK 2 from Homo sapiens

Seq: 524 a.a.

Struc: 13 a.a.

Enzyme reactions

• Enzyme class 2: Chains A, B, C, D: E.C.?
• Enzyme class 3: Chains E, F, H: 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⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

Nature 469:107-111 (2011)

PubMed id: 21170023

The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold.

A.S.Selyunin, S.E.Sutton, B.A.Weigele, L.E.Reddick, R.C.Orchard, S.M.Bresson, D.R.Tomchick, N.M.Alto.

ABSTRACT

The fidelity and specificity of information flow within a cell is controlled by scaffolding proteins that assemble and link enzymes into signalling circuits. These circuits can be inhibited by bacterial effector proteins that post-translationally modify individual pathway components. However, there is emerging evidence that pathogens directly organize higher-order signalling networks through enzyme scaffolding, and the identity of the effectors and their mechanisms of action are poorly understood. Here we identify the enterohaemorrhagic Escherichia coli O157:H7 type III effector EspG as a regulator of endomembrane trafficking using a functional screen, and report ADP-ribosylation factor (ARF) GTPases and p21-activated kinases (PAKs) as its relevant host substrates. The 2.5 Å crystal structure of EspG in complex with ARF6 shows how EspG blocks GTPase-activating-protein-assisted GTP hydrolysis, revealing a potent mechanism of GTPase signalling inhibition at organelle membranes. In addition, the 2.8 Å crystal structure of EspG in complex with the autoinhibitory Iα3-helix of PAK2 defines a previously unknown catalytic site in EspG and provides an allosteric mechanism of kinase activation by a bacterial effector. Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG, indicating its role as a 'catalytic scaffold' that effectively reprograms cellular events through the functional assembly of GTPase-kinase signalling complex.