Journal article
Entamoeba histolytica RacC Selectively Engages p21-Activated Kinase Effectors
Biochemistry (Easton), Vol.54(2), pp.404-412
01/20/2015
DOI: 10.1021/bi501226f
PMCID: PMC4303316
PMID: 25529118
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.
Details
- Title: Subtitle
- Entamoeba histolytica RacC Selectively Engages p21-Activated Kinase Effectors
- Creators
- Dustin E Bosch - University of North Carolina at Chapel HillDavid P Siderovski - West Virginia University
- Resource Type
- Journal article
- Publication Details
- Biochemistry (Easton), Vol.54(2), pp.404-412
- Publisher
- American Chemical Society
- DOI
- 10.1021/bi501226f
- PMID
- 25529118
- PMCID
- PMC4303316
- ISSN
- 0006-2960
- eISSN
- 1520-4995
- Grant note
- DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: F30DK091978; DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: GM082892
- Language
- English
- Date published
- 01/20/2015
- Academic Unit
- Pathology
- Record Identifier
- 9984199920002771
Metrics
6 Record Views