4MIT

Crystal structure of E. histolytica RacC bound to the EhPAK4 PBD

Summary for 4MIT

• Entry DOI: 10.2210/pdb4mit/pdb
• Descriptor: Rho family GTPase, Serine/threonine protein kinase PAK, putative, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: g domain, p21 binding domain, crib motif, hydrolase, signaling protein, kinase, gtp binding
• Biological source: Entamoeba histolytica; More
• Total number of polymer chains: 8
• Total formula weight: 114988.03

Authors

Bosch, D.E.,Siderovski, D.P. (deposition date: 2013-09-02, release date: 2014-09-03, Last modification date: 2023-09-20)

Primary citation

Bosch, D.E.,Siderovski, D.P.
Entamoeba histolytica RacC Selectively Engages p21-Activated Kinase Effectors.
Biochemistry, 54:404-412, 2015

PubMed Abstract: Rho family GTPases modulate actin cytoskeleton dynamics by signaling through multiple effectors, including the p21-activated kinases (PAKs). The intestinal parasite Entamoeba histolytica expresses ∼20 Rho family GTPases and seven isoforms of PAK, two of which have been implicated in pathogenesis-related processes such as amoebic motility and invasion and host cell phagocytosis. Here, we describe two previously unstudied PAK isoforms, EhPAK4 and EhPAK5, as highly specific effectors of EhRacC. A structural model based on 2.35 Å X-ray crystallographic data of a complex between EhRacC(Q65L)·GTP and the EhPAK4 p21 binding domain (PBD) reveals a fairly well-conserved Rho/effector interface despite deviation of the PBD α-helix. A structural comparison with EhRho1 in complex with EhFormin1 suggests likely determinants of Rho family GTPase signaling specificity in E. histolytica. These findings suggest a high degree of Rho family GTPase diversity and specificity in the single-cell parasite E. histolytica. Because PAKs regulate pathogenesis-related processes in E. histolytica, they may be valid pharmacologic targets for anti-amoebiasis drugs.

PubMed: 25529118
DOI: 10.1021/bi501226f

Experimental method

X-RAY DIFFRACTION (2.35 Å)