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* Residue conservation analysis
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PDB id:
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Protein transport/signaling protein
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Title:
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Crystal structure of a b30.2/spry domain-containing protein gustavus in complex with elongin b and elongin c
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Structure:
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Cg2944-pf, isoform f. Chain: a. Fragment: residues 28-253. Synonym: gustavus. Engineered: yes. Transcription elongation factor b polypeptide 2. Chain: b. Synonym: RNA polymerase ii transcription factor siii subunit b, siii p18, elongin b, elob, elongin 18 kda subunit.
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Source:
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Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. House mouse. Organism_taxid: 10090. Expression_system_taxid: 562
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Biol. unit:
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Trimer (from
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Resolution:
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1.80Å
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R-factor:
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0.218
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R-free:
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0.247
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Authors:
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J.S.Woo,B.H.Oh
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Key ref:
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J.S.Woo
et al.
(2006).
Structural and functional insights into the B30.2/SPRY domain.
EMBO J,
25,
1353-1363.
PubMed id:
DOI:
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Date:
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11-Jan-06
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Release date:
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21-Mar-06
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PROCHECK
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Headers
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References
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A1Z6E0
(GUS_DROME) -
Protein gustavus from Drosophila melanogaster
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Seq:
Struc:
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279 a.a.
217 a.a.
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Enzyme class:
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Chains A, B, C:
E.C.?
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DOI no:
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EMBO J
25:1353-1363
(2006)
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PubMed id:
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Structural and functional insights into the B30.2/SPRY domain.
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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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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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Selected figure(s)
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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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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.Kajaste-Rudnitski,
C.Pultrone,
F.Marzetta,
S.Ghezzi,
T.Coradin,
and
E.Vicenzi
(2010).
Restriction factors of retroviral replication: the example of Tripartite Motif (TRIM) protein 5 alpha and 22.
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Amino Acids,
39,
1-9.
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E.A.Gustafson,
and
G.M.Wessel
(2010).
Vasa genes: emerging roles in the germ line and in multipotent cells.
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Bioessays,
32,
626-637.
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J.M.Kugler,
C.Lem,
and
P.Lasko
(2010).
Reduced cul-5 activity causes aberrant follicular morphogenesis and germ cell loss in Drosophila oogenesis.
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PLoS One,
5,
e9048.
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J.M.Kugler,
J.S.Woo,
B.H.Oh,
and
P.Lasko
(2010).
Regulation of Drosophila vasa in vivo through paralogous cullin-RING E3 ligase specificity receptors.
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Mol Cell Biol,
30,
1769-1782.
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P.F.South,
I.M.Fingerman,
D.P.Mersman,
H.N.Du,
and
S.D.Briggs
(2010).
A conserved interaction between the SDI domain of Bre2 and the Dpy-30 domain of Sdc1 is required for histone methylation and gene expression.
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J Biol Chem,
285,
595-607.
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P.Filippakopoulos,
A.Low,
T.D.Sharpe,
J.Uppenberg,
S.Yao,
Z.Kuang,
P.Savitsky,
R.S.Lewis,
S.E.Nicholson,
R.S.Norton,
and
A.N.Bullock
(2010).
Structural basis for Par-4 recognition by the SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4.
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J Mol Biol,
401,
389-402.
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PDB codes:
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A.P.Mascarenhas,
and
K.Musier-Forsyth
(2009).
The capsid protein of human immunodeficiency virus: interactions of HIV-1 capsid with host protein factors.
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FEBS J,
276,
6118-6127.
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H.S.Tae,
N.C.Norris,
Y.Cui,
Y.Karunasekara,
P.G.Board,
A.F.Dulhunty,
and
M.G.Casarotto
(2009).
Molecular recognition of the disordered dihydropyridine receptor II-III loop by a conserved spry domain of the type 1 ryanodine receptor.
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Clin Exp Pharmacol Physiol,
36,
346-349.
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J.Jeong,
A.U.Rao,
J.Xu,
S.L.Ogg,
Y.Hathout,
C.Fenselau,
and
I.H.Mather
(2009).
The PRY/SPRY/B30.2 domain of butyrophilin 1A1 (BTN1A1) binds to xanthine oxidoreductase: implications for the function of BTN1A1 in the mammary gland and other tissues.
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J Biol Chem,
284,
22444-22456.
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J.N.Torimiro,
H.Javanbakht,
F.Diaz-Griffero,
J.Kim,
J.K.Carr,
M.Carrington,
J.Sawitzke,
D.S.Burke,
N.D.Wolfe,
M.Dean,
and
J.Sodroski
(2009).
A rare null allele potentially encoding a dominant-negative TRIM5alpha protein in Baka pygmies.
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Virology,
391,
140-147.
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L.M.van der Aa,
J.P.Levraud,
M.Yahmi,
E.Lauret,
V.Briolat,
P.Herbomel,
A.Benmansour,
and
P.Boudinot
(2009).
A large new subset of TRIM genes highly diversified by duplication and positive selection in teleost fish.
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BMC Biol,
7,
7.
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M.R.Neagu,
P.Ziegler,
T.Pertel,
C.Strambio-De-Castillia,
C.Grütter,
G.Martinetti,
L.Mazzucchelli,
M.Grütter,
M.G.Manz,
and
J.Luban
(2009).
Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components.
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J Clin Invest,
119,
3035-3047.
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S.Sebastian,
C.Grütter,
C.S.de Castillia,
T.Pertel,
S.Olivari,
M.G.Grütter,
and
J.Luban
(2009).
An invariant surface patch on the TRIM5alpha PRYSPRY domain is required for retroviral restriction but dispensable for capsid binding.
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J Virol,
83,
3365-3373.
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W.E.Johnson,
and
S.L.Sawyer
(2009).
Molecular evolution of the antiretroviral TRIM5 gene.
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Immunogenetics,
61,
163-176.
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Y.Cui,
H.S.Tae,
N.C.Norris,
Y.Karunasekara,
P.Pouliquin,
P.G.Board,
A.F.Dulhunty,
and
M.G.Casarotto
(2009).
A dihydropyridine receptor alpha1s loop region critical for skeletal muscle contraction is intrinsically unstructured and binds to a SPRY domain of the type 1 ryanodine receptor.
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Int J Biochem Cell Biol,
41,
677-686.
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A.K.Kar,
F.Diaz-Griffero,
Y.Li,
X.Li,
and
J.Sodroski
(2008).
Biochemical and biophysical characterization of a chimeric TRIM21-TRIM5alpha protein.
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J Virol,
82,
11669-11681.
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B.Balci-Peynircioglu,
A.L.Waite,
C.Hu,
N.Richards,
A.Staubach-Grosse,
E.Yilmaz,
and
D.L.Gumucio
(2008).
Pyrin, product of the MEFV locus, interacts with the proapoptotic protein, Siva.
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J Cell Physiol,
216,
595-602.
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B.J.Stanley,
E.S.Ehrlich,
L.Short,
Y.Yu,
Z.Xiao,
X.F.Yu,
and
Y.Xiong
(2008).
Structural insight into the human immunodeficiency virus Vif SOCS box and its role in human E3 ubiquitin ligase assembly.
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J Virol,
82,
8656-8663.
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PDB code:
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G.Brennan,
Y.Kozyrev,
and
S.L.Hu
(2008).
TRIMCyp expression in Old World primates Macaca nemestrina and Macaca fascicularis.
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Proc Natl Acad Sci U S A,
105,
3569-3574.
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J.Anderson,
and
R.Akkina
(2008).
Human immunodeficiency virus type 1 restriction by human-rhesus chimeric tripartite motif 5alpha (TRIM 5alpha) in CD34(+) cell-derived macrophages in vitro and in T cells in vivo in severe combined immunodeficient (SCID-hu) mice transplanted with human fetal tissue.
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Hum Gene Ther,
19,
217-228.
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J.Bonnefont,
S.I.Nikolaev,
A.L.Perrier,
S.Guo,
L.Cartier,
S.Sorce,
T.Laforge,
L.Aubry,
P.Khaitovich,
M.Peschanski,
S.E.Antonarakis,
and
K.H.Krause
(2008).
Evolutionary forces shape the human RFPL1,2,3 genes toward a role in neocortex development.
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Am J Hum Genet,
83,
208-218.
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J.G.Ryan,
and
R.Goldbach-Mansky
(2008).
The spectrum of autoinflammatory diseases: recent bench to bedside observations.
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Curr Opin Rheumatol,
20,
66-75.
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M.Sardiello,
S.Cairo,
B.Fontanella,
A.Ballabio,
and
G.Meroni
(2008).
Genomic analysis of the TRIM family reveals two groups of genes with distinct evolutionary properties.
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BMC Evol Biol,
8,
225.
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O.Okhrimenko,
and
I.Jelesarov
(2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
|
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J Mol Recognit,
21,
1.
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R.Higgs,
J.Ní Gabhann,
N.Ben Larbi,
E.P.Breen,
K.A.Fitzgerald,
and
C.A.Jefferies
(2008).
The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3.
|
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J Immunol,
181,
1780-1786.
|
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D.Ustek,
C.G.Ekmekci,
F.Selçukbiricik,
A.Cakiris,
B.Oku,
B.Vural,
H.Yanar,
K.Taviloglu,
U.Ozbek,
and
A.Gül
(2007).
Association between reduced levels of MEFV messenger RNA in peripheral blood leukocytes and acute inflammation.
|
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Arthritis Rheum,
56,
345-350.
|
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G.Brennan,
Y.Kozyrev,
T.Kodama,
and
S.L.Hu
(2007).
Novel TRIM5 isoforms expressed by Macaca nemestrina.
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J Virol,
81,
12210-12217.
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G.J.Towers
(2007).
The control of viral infection by tripartite motif proteins and cyclophilin A.
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Retrovirology,
4,
40.
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J.Luban
(2007).
Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection.
|
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J Virol,
81,
1054-1061.
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L.C.James,
A.H.Keeble,
Z.Khan,
D.A.Rhodes,
and
J.Trowsdale
(2007).
Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function.
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Proc Natl Acad Sci U S A,
104,
6200-6205.
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PDB code:
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P.V.Maillard,
S.Reynard,
F.Serhan,
P.Turelli,
and
D.Trono
(2007).
Interfering residues narrow the spectrum of MLV restriction by human TRIM5alpha.
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PLoS Pathog,
3,
e200.
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S.Sebastian,
and
J.Luban
(2007).
The Retroviral Restriction Factor TRIM5alpha.
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Curr Infect Dis Rep,
9,
167-173.
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T.Schaller,
S.Hué,
and
G.J.Towers
(2007).
An active TRIM5 protein in rabbits indicates a common antiviral ancestor for mammalian TRIM5 proteins.
|
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J Virol,
81,
11713-11721.
|
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J.J.Chae,
G.Wood,
S.L.Masters,
K.Richard,
G.Park,
B.J.Smith,
and
D.L.Kastner
(2006).
The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production.
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Proc Natl Acad Sci U S A,
103,
9982-9987.
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J.S.Woo,
H.Y.Suh,
S.Y.Park,
and
B.H.Oh
(2006).
Structural basis for protein recognition by B30.2/SPRY domains.
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Mol Cell,
24,
967-976.
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PDB code:
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S.L.Masters,
A.A.Lobito,
J.Chae,
and
D.L.Kastner
(2006).
Recent advances in the molecular pathogenesis of hereditary recurrent fevers.
|
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Curr Opin Allergy Clin Immunol,
6,
428-433.
|
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S.Ohkura,
M.W.Yap,
T.Sheldon,
and
J.P.Stoye
(2006).
All three variable regions of the TRIM5alpha B30.2 domain can contribute to the specificity of retrovirus restriction.
|
| |
J Virol,
80,
8554-8565.
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S.Yao,
M.S.Liu,
S.L.Masters,
J.G.Zhang,
J.J.Babon,
N.A.Nicola,
S.E.Nicholson,
and
R.S.Norton
(2006).
Dynamics of the SPRY domain-containing SOCS box protein 2: flexibility of key functional loops.
|
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Protein Sci,
15,
2761-2772.
|
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
