title: Different oligomeric properties and stability of highly homologous A1 and proto-oncogenic A2 variants of mammalian translation elongation factor eEF1.
abstract: Translation elongation factor 1A (eEF1A) directs aminoacyl-tRNA to the A site of 80S ribosomes. In addition, more than 97% homologous variants of eEF1A, A1 and A2, whose expression in different tissues is mutually exclusive, may fulfill a number of independent moonlighting functions in the cell; for instance, the unusual appearance of A2 in an A1-expressing tissue was recently linked to the induction of carcinogenesis. The structural background explaining the different functional performance of the highly homologous proteins is unclear. Here, the main difference in the structural properties of these proteins was revealed to be the improved ability of A1 to self-associate, as demonstrated by synchrotron small-angle X-ray scattering (SAXS) and analytical ultracentrifugation. Besides, the SAXS measurements at different urea concentrations revealed the low resistance of the A1 protein to urea. Titration of the proteins by hydrophobic dye 8-anilino-1-naphthalenesulfonate showed that the A1 isoform is more hydrophobic than A2. As the different association properties, lipophilicity, and stability of the highly similar eEF1A variants did not influence considerably their translation functions, at least in vitro, we suggest this difference may indicate a structural background for isoform-specific moonlighting roles.
authors.affiliation: Institute of Protein Research, RAS, Pushchino 142290, Russia. atim@vega.protres.ru
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Timchenko
authors.forename: Oleksandra V
authors.initials: OV
authors.lastname: Novosylna
authors.forename: Eugenij A
authors.initials: EA
authors.lastname: Prituzhalov
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kihara
authors.forename: Anna V
authors.initials: AV
authors.lastname: El'skaya
authors.forename: Boris S
authors.initials: BS
authors.lastname: Negrutskii
authors.forename: Igor N
authors.initials: IN
authors.lastname: Serdyuk
mesh_terms: D000595:Amino Acid Sequence; D000817:Anilino Naphthalenesulfonates / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D020648:Peptide Elongation Factor 1 / Q000737:chemistry* / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D011817:Rabbits; D012270:Ribosomes / Q000378:metabolism; D053838:Scattering, Small Angle; D013499:Surface Properties
chemical_list: C515594:8-anilino-1-naphthalenesulfonic acid; D000817:Anilino Naphthalenesulfonates; D020648:Peptide Elongation Factor 1; D020033:Protein Isoforms; D012346:RNA, Transfer, Amino Acyl