title: Glimmers in the midnight zone: characterization of aligned identical residues in sequence-dissimilar proteins sharing a common fold.
abstract: Sequence comparison of proteins that adopt the same fold has revealed a large degree of sequence variation. There are many pairs of structurally similar proteins with only a very low percentage of identical residues at structurally aligned positions. It is not clear whether these few identical residues have been conserved just by coincidence, or due to their structural and/or functional role The current study focuses on characterization of STructurally Aligned Identical ResidueS (STAIRS) in a data set of protein pairs that are structurally similar but sequentially dissimilar. The conservation pattern of the residues at structurally aligned positions has been characterized within the protein families of the two pair members, and mutually highly and weakly conserved positions of STAIRS could be identified About 40% of the STAIRS are only moderately conserved, suggesting that their maintenance may have been coincidental. The mutually highly conserved STAIRS show distinct features that are associated with protein structure and function: a relatively high fraction of these STAIRS are buried within their protein structures. Glycine, cysteine, histidine, and tryptophan are significantly over-represented among the mutually conserved STAIRS. A detailed survey of these STAIRS reveals residue-specific roles in the determination of the protein's structure and function.
authors.affiliation: Department of Molecular Genetics and Biotechnology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. idoerg@cc.huji.ac.il
authors.forename: I
authors.initials: I
authors.lastname: Friedberg
authors.forename: T
authors.initials: T
authors.lastname: Kaplan
authors.forename: H
authors.initials: H
authors.lastname: Margalit
mesh_terms: D000818:Animals; D016208:Databases, Factual; D006801:Humans; D017510:Protein Folding; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000145:classification / Q000235:genetics; D016415:Sequence Alignment / Q000379:methods*
chemical_list: D011506:Proteins