Journal article
A robust approach for analyzing a heterogeneous structural ensemble
Proteins, structure, function, and bioinformatics, Vol.73(4), pp.918-928
12/2008
Handle:
https://hdl.handle.net/2376/106795
PMID: 18536020
Abstract
Intrinsically unstructured proteins (IUP) are widespread in eukaryotes and participate in numerous cellular processes, but a structural explanation of the mechanisms they use to recognize and bind their diverse targets has proved elusive. Transcriptional activator domains are one class of IUP that function by recruiting other factors into basal transcription complexes. Transcriptional activator domains are known to use electrostatic interactions for recognition, but it is unclear how this could be accomplished by a structurally heterogeneous ensemble. To investigate this question, we performed principal component analysis on the atomic contact maps of an experimentally restrained ensemble of the human p53 transcriptional activator domain. This analysis revealed that the ensemble is conspicuously nonrandom and permitted a straightforward identification of persistent structural features and their relative probabilities. It was observed that six predominant long-range contacts are combinatorially arranged in 13 clusters of structures. Potential surfaces of the aligned clusters showed that these contacts uniformly organize the negative charges of the highly acidic p53 transcriptional activator domain on one face of the clusters. This observation provides a structural basis for the recruitment of other factors into basal transcription complexes and further supports the hypothesis that the structural ensembles of IUPs are not random and instead have evolved under selection to maintain specific structural features.
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Details
- Title
- A robust approach for analyzing a heterogeneous structural ensemble
- Creators
- David F Lowry - Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Life Science South, Moscow, Idaho 83844-3052, USAAndrew C HausrathGary W Daughdrill
- Publication Details
- Proteins, structure, function, and bioinformatics, Vol.73(4), pp.918-928
- Academic Unit
- Engineering and Applied Sciences (TRIC), School of
- Publisher
- United States
- Grant note
- P20 RR 16488 / NCRR NIH HHS P20 RR 16454-02 / NCRR NIH HHS
- Identifiers
- 99900546755201842
- Language
- English
- Resource Type
- Journal article