PDBsum entry 2iwg

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Immunoglobulin domain PDB id
Protein chains
207 a.a. *
181 a.a. *
FU4 ×2
Waters ×172
* Residue conservation analysis
PDB id:
Name: Immunoglobulin domain
Title: Complex between the pryspry domain of trim21 and igg fc
Structure: Ig gamma-1 chain c. Chain: a, d. Fragment: residues 120-326. Synonym: lj1. Engineered: yes. 52 kda ro protein. Chain: b, e. Fragment: residues 287-465. Synonym: lj1, sjoegren syndrome type a antigen, ss-a, ro,
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
2.35Å     R-factor:   0.217     R-free:   0.253
Authors: L.C.James,A.H.Keeble,D.A.Rhodes,J.Trowsdale
Key ref:
L.C.James et al. (2007). Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function. Proc Natl Acad Sci U S A, 104, 6200-6205. PubMed id: 17400754 DOI: 10.1073/pnas.0609174104
30-Jun-06     Release date:   27-Mar-07    
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Protein chains
Pfam   ArchSchema ?
P01857  (IGHG1_HUMAN) -  Ig gamma-1 chain C region
330 a.a.
207 a.a.
Protein chains
Pfam   ArchSchema ?
P19474  (RO52_HUMAN) -  E3 ubiquitin-protein ligase TRIM21
475 a.a.
181 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)


DOI no: 10.1073/pnas.0609174104 Proc Natl Acad Sci U S A 104:6200-6205 (2007)
PubMed id: 17400754  
Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function.
L.C.James, A.H.Keeble, Z.Khan, D.A.Rhodes, J.Trowsdale.
The human tripartite motif (TRIM) family comprises 70 members, including HIV restriction factor TRIM5alpha and disease-associated proteins TRIM20 (pyrin) and TRIM21. TRIM proteins have conserved domain architecture but diverse cellular roles. Here, we describe how the C-terminal PRYSPRY domain mediates diverse TRIM functions. The crystal structure of TRIM21 PRYSPRY in complex with its target IgG Fc reveals a canonical binding interface comprised of two discrete pockets formed by antibody-like variable loops. Alanine scanning of this interface has identified the hot-spot residues that control TRIM21 binding to Fc; the same hot-spots control HIV/murine leukemia virus restriction by TRIM5alpha and mediate severe familial Mediterranean fever in TRIM20/pyrin. Characterization of the IgG binding site for TRIM21 PRYSPRY reveals TRIM21 as a superantigen analogous to bacterial protein A and suggests that an antibody bipolar bridging mechanism may contribute to the pathogenic accumulation of anti-TRIM21 autoantibody immune complex in autoimmune disease.
  Selected figure(s)  
Figure 1.
Figure 4.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21205312 A.K.Kar, Y.Mao, G.Bird, L.Walensky, and J.Sodroski (2011).
Characterization of a core fragment of the rhesus monkey TRIM5α protein.
  BMC Biochem, 12, 1.  
21131187 F.W.McNab, R.Rajsbaum, J.P.Stoye, and A.O'Garra (2011).
Tripartite-motif proteins and innate immune regulation.
  Curr Opin Immunol, 23, 46-56.  
21455494 G.Zhao, D.Ke, T.Vu, J.Ahn, V.B.Shah, R.Yang, C.Aiken, L.M.Charlton, A.M.Gronenborn, and P.Zhang (2011).
Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces.
  PLoS Pathog, 7, e1002009.  
21294211 P.D.Griffiths, and R.S.Milne (2011).
Intracellular neutralisation of adenovirus by antibody.
  Rev Med Virol, 21, 1-2.  
21483490 S.Ohkura, D.C.Goldstone, M.W.Yap, K.Holden-Dye, I.A.Taylor, and J.P.Stoye (2011).
Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.
  PLoS Pathog, 7, e1002011.
PDB code: 2y4z
21045130 D.L.Mallery, W.A.McEwan, S.R.Bidgood, G.J.Towers, C.M.Johnson, and L.C.James (2010).
Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21).
  Proc Natl Acad Sci U S A, 107, 19985-19990.  
  20407604 P.D.Burbelo, K.H.Ching, B.L.Han, E.R.Bush, W.H.Reeves, and M.J.Iadarola (2010).
Extraordinary antigenicity of the human Ro52 autoantigen.
  Am J Transl Res, 2, 145-155.  
20561531 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.
  J Mol Biol, 401, 389-402.
PDB codes: 2jk9 2v24 3emw 3f2o
20357830 Q.T.Pham, A.Bouchard, M.G.Grütter, and L.Berthoux (2010).
Generation of human TRIM5alpha mutants with high HIV-1 restriction activity.
  Gene Ther, 17, 859-871.  
19825046 A.P.Mascarenhas, and K.Musier-Forsyth (2009).
The capsid protein of human immunodeficiency virus: interactions of HIV-1 capsid with host protein factors.
  FEBS J, 276, 6118-6127.  
19531472 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.
  J Biol Chem, 284, 22444-22456.  
19577266 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.
  Virology, 391, 140-147.  
19196451 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.
  BMC Biol, 7, 7.  
19494276 R.Yoshimi, T.H.Chang, H.Wang, T.Atsumi, H.C.Morse, and K.Ozato (2009).
Gene disruption study reveals a nonredundant role for TRIM21/Ro52 in NF-kappaB-dependent cytokine expression in fibroblasts.
  J Immunol, 182, 7527-7538.  
19153241 S.Sebastian, C.Grütter, 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.
  J Virol, 83, 3365-3373.  
19147168 S.U.Tareen, S.L.Sawyer, H.S.Malik, and M.Emerman (2009).
An expanded clade of rodent Trim5 genes.
  Virology, 385, 473-483.  
18761102 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.
  Int J Biochem Cell Biol, 41, 677-686.  
18420815 A.H.Keeble, Z.Khan, A.Forster, and L.C.James (2008).
TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved.
  Proc Natl Acad Sci U S A, 105, 6045-6050.
PDB codes: 2vok 2vol 3zo0
18799572 A.K.Kar, F.Diaz-Griffero, Y.Li, X.Li, and J.Sodroski (2008).
Biochemical and biophysical characterization of a chimeric TRIM21-TRIM5alpha protein.
  J Virol, 82, 11669-11681.  
18799573 C.R.Langelier, V.Sandrin, D.M.Eckert, D.E.Christensen, V.Chandrasekaran, S.L.Alam, C.Aiken, J.C.Olsen, A.K.Kar, J.G.Sodroski, and W.I.Sundquist (2008).
Biochemical characterization of a recombinant TRIM5alpha protein that restricts human immunodeficiency virus type 1 replication.
  J Virol, 82, 11682-11694.  
18177465 E.Fragouli, E.Eliopoulos, E.Petraki, P.Sidiropoulos, I.Aksentijevich, E.Galanakis, H.Kritikos, A.Repa, G.Fragiadakis, D.Boumpas, and G.N.Goulielmos (2008).
Familial Mediterranean Fever in Crete: a genetic and structural biological approach in a population of 'intermediate risk'.
  Clin Genet, 73, 152-159.  
18281860 J.G.Ryan, and R.Goldbach-Mansky (2008).
The spectrum of autoinflammatory diseases: recent bench to bedside observations.
  Curr Opin Rheumatol, 20, 66-75.  
18836477 K.Ozato, D.M.Shin, T.H.Chang, and H.C.Morse (2008).
TRIM family proteins and their emerging roles in innate immunity.
  Nat Rev Immunol, 8, 849-860.  
18768965 M.W.Richardson, R.G.Carroll, M.Stremlau, N.Korokhov, L.M.Humeau, G.Silvestri, J.Sodroski, and J.L.Riley (2008).
Mode of transmission affects the sensitivity of human immunodeficiency virus type 1 to restriction by rhesus TRIM5alpha.
  J Virol, 82, 11117-11128.  
18606080 R.L.Glaser, and R.Goldbach-Mansky (2008).
The spectrum of monogenic autoinflammatory syndromes: understanding disease mechanisms and use of targeted therapies.
  Curr Allergy Asthma Rep, 8, 288-298.  
  17565686 G.J.Towers (2007).
The control of viral infection by tripartite motif proteins and cyclophilin A.
  Retrovirology, 4, 40.  
17848512 P.A.Ramsland, N.Willoughby, H.M.Trist, W.Farrugia, P.M.Hogarth, J.D.Fraser, and B.D.Wines (2007).
Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1.
  Proc Natl Acad Sci U S A, 104, 15051-15056.
PDB code: 2qej
18166079 P.V.Maillard, S.Reynard, F.Serhan, P.Turelli, and D.Trono (2007).
Interfering residues narrow the spectrum of MLV restriction by human TRIM5alpha.
  PLoS Pathog, 3, e200.  
18159944 S.L.Sawyer, M.Emerman, and H.S.Malik (2007).
Discordant evolution of the adjacent antiretroviral genes TRIM22 and TRIM5 in mammals.
  PLoS Pathog, 3, e197.  
17728224 T.Schaller, S.Hué, and G.J.Towers (2007).
An active TRIM5 protein in rabbits indicates a common antiviral ancestor for mammalian TRIM5 proteins.
  J Virol, 81, 11713-11721.  
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 code is shown on the right.