title: A new family of β-helix proteins with similarities to the polysaccharide lyases.
abstract: Microorganisms that degrade biomass produce diverse assortments of carbohydrate-active enzymes and binding modules. Despite tremendous advances in the genomic sequencing of these organisms, many genes do not have an ascribed function owing to low sequence identity to genes that have been annotated. Consequently, biochemical and structural characterization of genes with unknown function is required to complement the rapidly growing pool of genomic sequencing data. A protein with previously unknown function (Cthe_2159) was recently isolated in a genome-wide screen using phage display to identify cellulose-binding protein domains from the biomass-degrading bacterium Clostridium thermocellum. Here, the crystal structure of Cthe_2159 is presented and it is shown that it is a unique right-handed parallel β-helix protein. Despite very low sequence identity to known β-helix or carbohydrate-active proteins, Cthe_2159 displays structural features that are very similar to those of polysaccharide lyase (PL) families 1, 3, 6 and 9. Cthe_2159 is conserved across bacteria and some archaea and is a member of the domain of unknown function family DUF4353. This suggests that Cthe_2159 is the first representative of a previously unknown family of cellulose and/or acid-sugar binding β-helix proteins that share structural similarities with PLs. Importantly, these results demonstrate how functional annotation by biochemical and structural analysis remains a critical tool in the characterization of new gene products.
authors.affiliation: Bioscience Division, Los Alamos National Laboratory, MS888, Los Alamos, NM 87545, USA.
authors.forename: Devin W
authors.initials: DW
authors.lastname: Close
authors.affiliation: New Mexico Consortium, Los Alamos, NM 87544, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: D'Angelo
authors.affiliation: Bioscience Division, Los Alamos National Laboratory, MS888, Los Alamos, NM 87545, USA.
authors.forename: Andrew R M
authors.initials: AR
authors.lastname: Bradbury
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002482:Cellulose / Q000378:metabolism; D003001:Cloning, Molecular; D048013:Acetivibrio thermocellus / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D005682:Gadolinium / Q000737:chemistry; D008958:Models, Molecular; D011133:Polysaccharide-Lyases / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D002482:Cellulose; D005682:Gadolinium; D011133:Polysaccharide-Lyases; D002118:Calcium
keywords: Clostridium thermocellum; biomass degradation; cellulose; domain of unknown function; functional annotation; gadolinium; genome filtering; pectate; pectin; phage display; polysaccharide lyase; β-helix