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PDBsum entry 2fnj
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Protein transport/signaling protein
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PDB id
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2fnj
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References listed in PDB file
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Key reference
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Title
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Structural and functional insights into the b30.2/spry domain.
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Authors
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J.S.Woo,
J.H.Imm,
C.K.Min,
K.J.Kim,
S.S.Cha,
B.H.Oh.
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Ref.
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EMBO J, 2006,
25,
1353-1363.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Figure 1 Structure of the GUS:ElonginBC complex. (A) Ribbon
drawing of the GUS:ElonginBC complex. The  -helices
of GUS are in either red or magenta (for BC box), sheet A in
orange, and sheet B in green. The domain organization of
GUSTAVUS is shown. The region in yellow on the diagram indicates
the fragment of the protein used for the structure
determination. (B) Ribbon drawing of the B30.2/SPRY domain of
GUS. The secondary structural elements are sequentially labeled
and colored as in (A). The SPRY domain in GUS is indicated by
color-coding the secondary structural elements.
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Figure 3.
Figure 3 Sequence variations or mutations in TRIM5 ,
Pyrin, and MID1. (A) Location on the primary structures. The
diagrams depict the primary structures of the three proteins and
the domains they possess. The locations of the sequence
variations or disease-causing mutations are marked on the
diagrams for TRIM5 :
pink triangles, locations of the significant sequence variation
and length polymorphism in primate TRIM5 proteins;
pink arrow, the substitution of R332P in human TRIM5 that
confers the ability to restrict HIV-1, for Pyrin: blue arrows,
the FMF-causing point mutations including three mutational hot
spots marked with an asterisk, and for MID1: white arrows, the
OS-causing frame shift or nonsense mutations; yellow arrows,
point mutations, insertion, or deletion of amino acids. (B)
Location of the corresponding residues of GUS on the tertiary
structure. The sequence variations or mutations in the three
proteins are mapped on the structure of the B30.2/SPRY domain of
GUS. The mutation sites are indicated by large C atom
spheres and labels shown in the same color of the arrows in (A).
The residues of GUS corresponding to the mutation points are in
the parentheses. The loop regions in pink correspond to the
locations of the length polymorphism in the primate TRIM5 proteins.
'Insertion' stands for the eight amino-acid insertional mutation
in MID1, and 'del' stands for deletion of a residue in Pyrin. A
schematic drawing of the  -sandwich
structure of GUS is shown to aid the recognition of surface A
and surface B.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
EMBO J
(2006,
25,
1353-1363)
copyright 2006.
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