title: Organization of the multiaminoacyl-tRNA synthetase complex and the cotranslational protein folding.
abstract: Aminoacyl-tRNA synthetases (ARSs) play an essential role in the protein synthesis by catalyzing an attachment of their cognate amino acids to tRNAs. Unlike their prokaryotic counterparts, ARSs in higher eukaryotes form a multiaminoacyl-tRNA synthetase complex (MARS), consisting of the subset of ARS polypeptides and three auxiliary proteins. The intriguing feature of MARS complex is the presence of only nine out of twenty ARSs, specific for Arg, Asp, Gln, Glu, Ile, Leu, Lys, Met, and Pro, regardless of the organism, cell, or tissue types. Although existence of MARSs complex in higher eukaryotes has been already known for more than four decades, its functional significance remains elusive. We found that seven of the nine corresponding amino acids (Arg, Gln, Glu, Ile, Leu, Lys, and Met) together with Ala form a predictor of the protein α-helicity. Remarkably, all amino acids (besides Ala) in the predictor have the highest possible number of side-chain rotamers. Therefore, compositional bias of a typical α-helix can contribute to the helix's stability by increasing the entropy of the folded state. It also appears that position-specific α-helical propensity, specifically periodic alternation of charged and hydrophobic residues in the helices, may well be provided by the structural organization of the complex. Considering characteristics of MARS complex from the perspective of the α-helicity, we hypothesize that specific composition and structure of the complex represents a functional mechanism for coordination of translation with the fast and correct folding of amphiphilic α-helices.
authors.affiliation: Bioinformatics Institute (BII), Agency for Science, Technology and Research (a*STAR), Singapore, 138671.|Department of Biological Sciences (DBS), National University of Singapore (NUS), Singapore, 117579.
authors.forename: Igor N
authors.initials: IN
authors.lastname: Berezovsky
authors.affiliation: Bioinformatics Institute (BII), Agency for Science, Technology and Research (a*STAR), Singapore, 138671.
authors.forename: Zejun
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: RIKEN Center for Sustainable Resource Science (CSRS), Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurotani
authors.affiliation: Research Center for Environmental Genomics, Kobe University, Kobe, Japan.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Tokmakov
authors.affiliation: Bioinformatics Institute (BII), Agency for Science, Technology and Research (a*STAR), Singapore, 138671.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Kurochkin
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry; D017510:Protein Folding; D046188:Protein Modification, Translational; D017433:Protein Structure, Secondary
chemical_list: D000596:Amino Acids; D010446:Peptide Fragments; D000604:Amino Acyl-tRNA Synthetases
keywords: amphiphilic α-helices; cotranslational folding; multiaminoacyl-tRNA synthetase complex (MARS); predictor of α-helicity; side-chain rotamers