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Structural and functional insights into the B30.2/SPRY domain
Author(s) -
Woo JaeSung,
Imm JoonHyuk,
Min ChangKi,
Kim KyungJin,
Cha SunShin,
Oh ByungHa
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600994
Subject(s) - biology , computational biology , domain (mathematical analysis) , genetics , evolutionary biology , mathematics , mathematical analysis
The B30.2/SPRY domain is present in ∼700 eukaryotic (∼150 human) proteins, including medically important proteins such as TRIM5α 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 β‐sandwich core structure of its B30.2/SPRY domain. Ensuing studies identified one end of the β‐sandwich as the surface interacting with an RNA helicase VASA with a 40 nM dissociation constant. The sequence variation in TRIM5α 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.