Regions of intrinsic disorder help identify a novel nuclear localization signal in Toxoplasma gondii histone acetyltransferase TgGCN5-B.
We have previously shown that protozoan parasites, such as Toxoplasma gondii, contain a high prevalence of intrinsically disordered regions in their predicted proteins. Here, we determine that both TgGCN5-family histone acetyltransferases (HATs) contain unusually high levels of intrinsic disorder. A previously identified basic-rich nuclear localization signal (NLS) in the N-terminus of TgGCN5-A is located within such a region of predicted disorder, but this NLS is not conserved in TgGCN5-B. We therefore analyzed the intrinsically disordered regions of TgGCN5-B for basic-rich sequences that could be indicative of a functional NLS, and this led to the identification of a novel NLS for TgGCN5-B, RPAENKKRGR. The functionality of the GCN5-B NLS was validated experimentally and has predictive value. These studies demonstrate that basic-rich sequences within regions predicted to be intrinsically disordered constitute criteria for a candidate NLS.
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Stacy E
SE
Dixon
Micah M
MM
Bhatti
Vladimir N
VN
Uversky
A Keith
AK
Dunker
William J
WJ
Sullivan
D019295:Computational Biology / Q000379:methods; D051548:Histone Acetyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D019913:Nuclear Localization Signals; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D051548:Histone Acetyltransferases; D019913:Nuclear Localization Signals; D015800:Protozoan Proteins; C402103:GCN5 protein, Toxoplasma gondii; D000099224:p300-CBP-Associated Factor