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Sequence and structural analysis of cellular retinoic acid‐binding proteins reveals a network of conserved hydrophobic interactions
Author(s) -
Gunasekaran Kannan,
Hagler Arnold T.,
Gierasch Lila M.
Publication year - 2003
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10520
Subject(s) - conserved sequence , amino acid , biology , folding (dsp implementation) , protein data bank (rcsb pdb) , protein folding , peptide sequence , protein family , protein structure , binding site , sequence (biology) , protein secondary structure , computational biology , biochemistry , gene , electrical engineering , engineering
Abstract Proteins in the intracellular lipid‐binding protein (iLBP) family show remarkably high structural conservation despite their low‐sequence identity. A multiple‐sequence alignment using 52 sequences of iLBP family members revealed 15 fully conserved positions, with a disproportionately high number of these (n=7) located in the relatively small helical region. The conserved positions displayed high structural conservation based on comparisons of known iLBP crystal structures. It is striking that the β‐sheet domain had few conserved positions, despite its high structural conservation. This observation prompted us to analyze pair‐wise interactions within the β‐sheet region to ask whether structural information was encoded in interacting amino acid pairs. We conducted this analysis on the iLBP family member, cellular retinoic acid‐binding protein I (CRABP I), whose folding mechanism is under study in our laboratory. Indeed, an analysis based on a simple classification of hydrophobic and polar amino acids revealed a network of conserved interactions in CRABP I that cluster spatially, suggesting a possible nucleation site for folding. Significantly, a small number of residues participated in multiple conserved interactions, suggesting a key role for these sites in the structure and folding of CRABP I. The results presented here correlate well with available experimental evidence on folding of CRABPs and their family members and suggest future experiments. The analysis also shows the usefulness of considering pair‐wise conservation based on a simple classification of amino acids, in analyzing sequences and structures to find common core regions among homologues. Proteins 2003. © 2003 Wiley‐Liss, Inc.