3PCS

Structure of EspG-PAK2 autoinhibitory Ialpha3 helix complex

3PCS の概要

• エントリーDOI: 10.2210/pdb3pcs/pdb
• 関連するPDBエントリー: 3PCR
• 分子名称: EspG, Serine/threonine-protein kinase PAK 2 (2 entities in total)
• 機能のキーワード: bacterial effector, kinase, autoinhibitory ialpha3 helix, protein transport-transferase complex, protein transport/transferase
• 由来する生物種: Escherichia coli; 詳細
• 細胞内の位置: Secreted : Q7DB50; Serine/threonine-protein kinase PAK 2: Cytoplasm. PAK-2p34: Nucleus: Q13177
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 165814.14

構造登録者

Tomchick, D.R.,Alto, N.M.,Selyunin, A.S. (登録日: 2010-10-21, 公開日: 2011-01-05, 最終更新日: 2023-09-06)

主引用文献

Selyunin, A.S.,Sutton, S.E.,Weigele, B.A.,Reddick, L.E.,Orchard, R.C.,Bresson, S.M.,Tomchick, D.R.,Alto, N.M.
The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold.
Nature, 469:107-111, 2011

PubMed 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.

PubMed: 21170023
DOI: 10.1038/nature09593

実験手法

X-RAY DIFFRACTION (2.86 Å)