title: Structural basis for protein recognition by B30.2/SPRY domains.
abstract: B30.2/SPRY domains are found in numerous proteins that cover a wide spectrum of biological functions, including regulation of cytokine signaling and innate retroviral restriction. Herein, we report the crystal structure of the B30.2/SPRY domain of a SPRY domain-containing SOCS box (SSB) protein, GUSTAVUS, complexed with a 20 amino acid peptide derived from the RNA helicase VASA, revealing how these domains recognize target proteins. The peptide-binding site is conformationally rigid and has a preformed pocket. The interaction between the pocket and the Asp-Ile-Asn-Asn-Asn-Asn sequence within the peptide accounts for the high-affinity binding between GUSTAVUS and VASA. This observation led to a facile identification of the Glu-Leu-Asn-Asn-Asn-Leu sequence as the recognition motif in a proapoptotic protein Par-4 for its interaction with a GUSTAVUS homolog, SSB-1. Ensuing analyses indicated that many B30.2/SPRY domains have a similar preformed pocket, which would allow them to bind multiple targets.
authors.affiliation: Center for Biomolecular Recognition, Department of Life Sciences, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, 790-784, Korea.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Woo
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Suh
authors.forename: Sam-Yong
authors.initials: SY
authors.lastname: Park
authors.forename: Byung-Ha
authors.initials: BH
authors.lastname: Oh
mesh_terms: D000595:Amino Acid Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D003460:Crystallization; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D029721:Drosophila Proteins; D008024:Ligands; C109768:PDP1 protein, Drosophila; C470130:gus protein, Drosophila