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PMID: 16498413 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Structural and functional insights into the B30.2/SPRY domain.

The EMBO journal ·Vol. 25 ·No. 6 ·2006-03-22 ·Pages 1353-63

Woo JS, Imm JH, Min CK, Kim KJ, Cha SS, Oh BH

Abstract

The B30.2/SPRY domain is present in approximately 700 eukaryotic (approximately 150 human) proteins, including medically important proteins such as TRIM5alpha and Pyrin. Nonetheless, the functional role of this modular domain remained unclear. Here, we report the crystal structure of an SPRY-SOCS box family protein GUSTAVUS in complex with Elongins B and C, revealing a highly distorted two-layered beta-sandwich core structure of its B30.2/SPRY domain. Ensuing studies identified one end of the beta-sandwich as the surface interacting with an RNA helicase VASA with a 40 nM dissociation constant. The sequence variation in TRIM5alpha responsible for HIV-1 restriction and most of the mutations in Pyrin causing familial Mediterranean fever map on this surface, implicating the corresponding region in many B30.2/SPRY domains as the ligand-binding site. The amino acids lining the binding surface are highly variable among the B30.2/SPRY domains, suggesting that these domains are protein-interacting modules, which recognize a specific individual partner protein rather than a consensus sequence motif.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Animals Binding Sites Carrier Proteins/chemistry,genetics Cytoskeletal Proteins/chemistry DEAD-box RNA Helicases Drosophila Proteins/chemistry,genetics,metabolism Elongin Ligands Models, Molecular Molecular Sequence Data Mutation/genetics Protein Binding Protein Conformation Protein Folding Protein Structure, Tertiary Pyrin RNA Helicases/genetics,metabolism Sequence Homology, Amino Acid Transcription Factors/chemistry,genetics
Chemicals
Carrier Proteins Cytoskeletal Proteins Drosophila Proteins Elongin Ligands MEFV protein, human Pyrin Transcription Factors gus protein, Drosophila vas protein, Drosophila DEAD-box RNA Helicases RNA Helicases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Woo Jae-Sung
Division of Molecular and Life Sciences, Department of Life Sciences, Center for Biomolecular Recognition, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea.
Imm Joon-Hyuk
Min Chang-Ki
Kim Kyung-Jin
Cha Sun-Shin
Oh Byung-Ha
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
2006-03-22
Epub
2006-00-23
Pages
1353-63
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1422157
Subset
IM
Databases
GENBANK
AAA17031, AAB64200, AAH10861, CAH72715
RefSeq
NP_000234, NP_001723, NP_003189, NP_003736, NP_006360, NP_056441, NP_057198, NP_065901, NP_079382, NP_149023, NP_150632, NP_477514, NP_724402, XP_117294
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