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PDBsum entry 2vok

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protein Protein-protein interface(s) links
Immune system PDB id
2vok
Jmol
Contents
Protein chains
186 a.a. *
Waters ×481
* Residue conservation analysis
PDB id:
2vok
Name: Immune system
Title: Murine trim21
Structure: 52 kda ro protein. Chain: a, b. Synonym: trim21, sjoegren syndrome type a antigen, ss-a, ro(ss-a), 52 kda ribonucleoprotein autoantigen ro/ss-a, tripartite motif-containing protein 21. Engineered: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.30Å     R-factor:   0.215     R-free:   0.236
Authors: A.H.Keeble,Z.Khan,A.Forster,L.C.James
Key ref:
A.H.Keeble et al. (2008). TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved. Proc Natl Acad Sci U S A, 105, 6045-6050. PubMed id: 18420815 DOI: 10.1073/pnas.0800159105
Date:
19-Feb-08     Release date:   15-Apr-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q62191  (RO52_MOUSE) -  E3 ubiquitin-protein ligase TRIM21
Seq:
Struc:
470 a.a.
186 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

 

 
DOI no: 10.1073/pnas.0800159105 Proc Natl Acad Sci U S A 105:6045-6050 (2008)
PubMed id: 18420815  
 
 
TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved.
A.H.Keeble, Z.Khan, A.Forster, L.C.James.
 
  ABSTRACT  
 
The newly identified tripartite motif (TRIM) family of proteins mediate innate immunity and other critical cellular functions. Here we show that TRIM21, which mediates the autoimmune diseases rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome, is a previously undescribed IgG receptor with a binding mechanism unlike known mammalian Fcgamma receptors. TRIM21 simultaneously targets conserved hot-spot residues on both Ig domains of the Fc fragment using a PRYSPRY domain with a preformed multisite interface. The binding sites on both TRIM21 and Fc are highly conserved to the extent that the proteins are functionally interchangeable through murine, canine, primate, and human species. Pre-steady-state analysis exposes mechanistic conservation at the level of individual residues, which make the same energetic and kinetic contributions to binding despite varying in sequence. Together, our results reveal that TRIM21 is a previously undescribed type of IgG receptor based on a non-Ig scaffold whose interaction at the fundamental level-structural, thermodynamic, and kinetic-is evolutionarily conserved.
 
  Selected figure(s)  
 
Figure 4.
Effect of site-directed mutagenesis on cognate versus noncognate species TRIM21:IgG interaction. When the effects of mouse TRIM21 mutations on binding mouse IgG (cognate; x axis) are plotted against the effect on binding human IgG (noncognate; y axis) there exists a striking linear correlation (R ^2 = 0.98) suggesting that the same interactions are used to stabilize both complexes.
Figure 6.
Comparison of mouse and human TRIM21. (Left) Superposition of mouse (orange) and human (yellow) PRYSPRY domains. Where the sequences diverge the annotations are formatted so that the first residue is for human and the second is for mouse; e.g., D/S326 indicates an aspartic acid in human and a serine in mouse. (Right) Superposition of mouse (red and orange) and human (pink and yellow) complexes with Fc.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
20227114 K.H.Ching, P.D.Burbelo, P.J.Carlson, W.C.Drevets, and M.J.Iadarola (2010).
High levels of Anti-GAD65 and Anti-Ro52 autoantibodies in a patient with major depressive disorder showing psychomotor disturbance.
  J Neuroimmunol, 222, 87-89.  
  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.  
19073742 L.M.Ylinen, T.Schaller, A.Price, A.J.Fletcher, M.Noursadeghi, L.C.James, and G.J.Towers (2009).
Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D.
  J Virol, 83, 2044-2047.  
19930592 M.Gautier, L.Flori, A.Riebler, F.Jaffrézic, D.Laloé, I.Gut, K.Moazami-Goudarzi, and J.L.Foulley (2009).
A whole genome Bayesian scan for adaptive genetic divergence in West African cattle.
  BMC Genomics, 10, 550.  
19302049 S.L.Masters, A.Simon, I.Aksentijevich, and D.L.Kastner (2009).
Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*).
  Annu Rev Immunol, 27, 621-668.  
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.  
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.