title: Prioritizing targets for structural biology through the lens of proteomics: the archaeal protein TGAM_1934 from Thermococcus gammatolerans.
abstract: ORFans are hypothetical proteins lacking any significant sequence similarity with other proteins. Here, we highlighted by quantitative proteomics the TGAM_1934 ORFan from the hyperradioresistant Thermococcus gammatolerans archaeon as one of the most abundant hypothetical proteins. This protein has been selected as a priority target for structure determination on the basis of its abundance in three cellular conditions. Its solution structure has been determined using multidimensional heteronuclear NMR spectroscopy. TGAM_1934 displays an original fold, although sharing some similarities with the 3D structure of the bacterial ortholog of frataxin, CyaY, a protein conserved in bacteria and eukaryotes and involved in iron-sulfur cluster biogenesis. These results highlight the potential of structural proteomics in prioritizing ORFan targets for structure determination based on quantitative proteomics data. The proteomic data and structure coordinates have been deposited to the ProteomeXchange with identifier PXD000402 (http://proteomecentral.proteomexchange.org/dataset/PXD000402) and Protein Data Bank under the accession number 2mcf, respectively.
authors.affiliation: Centre de Biochimie Structurale, Universités de Montpellier, Montpellier, France.
authors.forename: Yin-Shan
authors.initials: YS
authors.lastname: Yang
authors.forename: Bernard
authors.initials: B
authors.lastname: Fernandez
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lagorce
authors.forename: Valérie
authors.initials: V
authors.lastname: Aloin
authors.forename: Karine Montet
authors.initials: KM
authors.lastname: De Guillen
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Boyer
authors.forename: Alain
authors.initials: A
authors.lastname: Dedieu
authors.forename: Fabrice
authors.initials: F
authors.lastname: Confalonieri
authors.forename: Jean
authors.initials: J
authors.lastname: Armengaud
authors.forename: Christian
authors.initials: C
authors.lastname: Roumestand
mesh_terms: D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry*; D033862:Iron-Binding Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D040901:Proteomics; D019712:Thermococcus / Q000737:chemistry*; D000096923:Frataxin
chemical_list: D019843:Archaeal Proteins; D033862:Iron-Binding Proteins; D000096923:Frataxin
keywords: Genome annotation; High-throughput proteomics; Microbiology; NMR structure; ORFan; Protein evolution