Several families of proteins are under investigation for the determination of the relationships between structure and function. Most of these protein families are eukaryotic nuclear proteins and have the property of binding to DNA or RNA, for example, the histone proteins, the HMG-1 box proteins, heat shock factors, ets proteins, HMG-I proteins, and ribosomal proteins. As an example, the HMG-1 box family of proteins is not highly conserved and is represented by over 100 examples in the sequence databases. We have identified a signature for this family of proteins and have classified them into several groups according to their sequence and functional relation. In the past few years, numerous proteins have been identified as containing a stretch of about 75 amino acids which are homologous to an abundant non-histone chromosomal protein HMG-1. These proteins bind DNA and bends it on binding or bind preferentially to bent DNA. Several of these proteins have been implicated in numerous nuclear functions including transcription, replication, and chromatin structure as well as transcription regulation in mitochondria resulting, in some cases, in such phenotypes as sex and mating type determination. For example, we have compiled a database of the HMG-1 box family of proteins and are analyzing the sequences to determine the phylogeny between these functionally widely-diverse proteins. The 3D structure of several HMG-1 box domains have been determined by multi-dimensional NMR. We have used one of these structure to model the other members of the family by a threading method. We have successfully produced models for the complete family of HMG-1 box domains. The conclusion drawn from these calculations is that these proteins are mostly likely to fold into similar conformations. Iterative motif search algorithms are being used to detect new and as yet unidentified motifs of several families of DNA-binding and RNA-binding proteins. In a separate project, we have identified several proteins which contain domains which could be related to the histone fold in the nucleosome octamer. We have identified conserved residues in all the histone proteins and related the conservation to the protein-protein and protein-DNA contact preservation in the histone folds in nucleosomes. We have developed and updated the Histone Database for researchers to obtain curated sequence alignments of the histone proteins and histone fold containg proteins and recently we have identified bacterial proteins which contain the histone fold.

Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2012
Total Cost
$78,092
Indirect Cost
Name
National Library of Medicine
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DUNS #
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Xiao, Hua; Wang, Feng; Wisniewski, Jan et al. (2017) Molecular basis of CENP-C association with the CENP-A nucleosome at yeast centromeres. Genes Dev 31:1958-1972
El Kennani, Sara; Adrait, Annie; Shaytan, Alexey K et al. (2017) MS_HistoneDB, a manually curated resource for proteomic analysis of human and mouse histones. Epigenetics Chromatin 10:2
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