title: The crystal structure of ORF-9b, a lipid binding protein from the SARS coronavirus.
abstract: To achieve the greatest output from their limited genomes, viruses frequently make use of alternative open reading frames, in which translation is initiated from a start codon within an existing gene and, being out of frame, gives rise to a distinct protein product. These alternative protein products are, as yet, poorly characterized structurally. Here we report the crystal structure of ORF-9b, an alternative open reading frame within the nucleocapsid (N) gene from the SARS coronavirus. The protein has a novel fold, a dimeric tent-like beta structure with an amphipathic surface, and a central hydrophobic cavity that binds lipid molecules. This cavity is likely to be involved in membrane attachment and, in mammalian cells, ORF-9b associates with intracellular vesicles, consistent with a role in the assembly of the virion. Analysis of ORF-9b and other overlapping genes suggests that they provide snapshots of the early evolution of novel protein folds.
authors.affiliation: Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Oxford University, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
authors.forename: Christoph
authors.initials: C
authors.lastname: Meier
authors.forename: A Radu
authors.initials: AR
authors.lastname: Aricescu
authors.forename: Rene
authors.initials: R
authors.lastname: Assenberg
authors.forename: Robin T
authors.initials: RT
authors.lastname: Aplin
authors.forename: Robert J C
authors.initials: RJ
authors.lastname: Gilbert
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Grimes
authors.forename: David I
authors.initials: DI
authors.lastname: Stuart
mesh_terms: D000595:Amino Acid Sequence; D002213:Capsid / Q000648:ultrastructure; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D036022:Capsid Proteins