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PDBsum entry 2uwi

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protein Protein-protein interface(s) links
Receptor PDB id
2uwi
Jmol
Contents
Protein chains
127 a.a. *
Waters ×192
* Residue conservation analysis
PDB id:
2uwi
Name: Receptor
Title: Structure of crme, a poxvirus tnf receptor
Structure: Crme protein. Chain: a, b. Fragment: cysteine-rich domains 1-3, residues 22-153. Synonym: cytokine response modifier e. Engineered: yes
Source: Vaccinia virus. Organism_taxid: 10252. Strain: lister. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.00Å     R-factor:   0.210     R-free:   0.246
Authors: S.C.Graham,M.W.Bahar,N.G.Abrescia,G.L.Smith,D.I.Stuart, J.M.Grimes
Key ref:
S.C.Graham et al. (2007). Structure of CrmE, a Virus-encoded Tumour Necrosis Factor Receptor. J Mol Biol, 372, 660-671. PubMed id: 17681535 DOI: 10.1016/j.jmb.2007.06.082
Date:
22-Mar-07     Release date:   10-Jul-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q8UYL3  (Q8UYL3_9POXV) -  CrmE protein
Seq:
Struc:
167 a.a.
127 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/j.jmb.2007.06.082 J Mol Biol 372:660-671 (2007)
PubMed id: 17681535  
 
 
Structure of CrmE, a Virus-encoded Tumour Necrosis Factor Receptor.
S.C.Graham, M.W.Bahar, N.G.Abrescia, G.L.Smith, D.I.Stuart, J.M.Grimes.
 
  ABSTRACT  
 
Vaccinia virus (VACV), the smallpox vaccine, encodes many proteins that subvert the host immune response. One of these, cytokine response modifier E (CrmE), is secreted by infected cells and protects these cells from apoptotic challenge by tumour necrosis factor alpha (TNFalpha). We have expressed recombinant CrmE from VACV strain Lister in Escherichia coli, shown that the purified protein is monomeric in solution and competent to bind TNFalpha, and solved the structure to 2.0 A resolution. This is the first structure of a virus-encoded tumour necrosis factor receptor (TNFR). CrmE shares significant sequence similarity with mammalian type 2 TNF receptors (TNFSFR1B, p75; TNFR type 2). The structure confirms that CrmE adopts the canonical TNFR fold but only one of the two "ligand-binding" loops of TNFRSF1A is conserved in CrmE, suggesting a mechanism for the higher affinity of poxvirus TNFRs for TNFalpha over lymphotoxin-alpha. The roles of dimerisation and pre-ligand-assembly domains (PLADs) in poxvirus and mammalian TNFR activity are discussed.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. The structure of VACV CrmE. (a) Cartoon representation of CrmE, ramp coloured from blue at the N terminus (residue 22) to red at the C terminus (residue 148). All molecular Figures were produced using PyMOL [http://pymol.sourceforge.net/]. (b) Domain structure of CrmE. CrmE is shown in a ribbon representation with CRDs 1–3 coloured blue, green and red, respectively. The sulphur atoms that form the nine intra-domain disulphide bonds are shown as yellow spheres. (c) Alignment of the sequences of CRDs 1–3 from a representative set of human and poxvirus TNFRs that interact with TNFα. Black lines above the alignment denote the CRD sub-modules (nomenclature by Naismith & Sprang^20). Numbering above the sequences corresponds to CrmE residue numbers. Cysteine residues that form disulphide bonds are highlighted in yellow, and yellow lines below the alignment represent the disulphide bonding topology. Cysteine residues that form the second disulphide bond of the TNFRSF1A CRD3 B2 module are highlighted in orange, residues that were mutated to abolish PLAD activity in TNFRSF1A are highlighted in magenta,^28 and other conserved residues are highlighted in blue. Species and UNIPROT IDs are as follows: CrmE, VACV CrmE (Q8UYL3); CrmB, variola virus CrmB (P34015); CrmC, VACV CrmC (Q911R5); CrmD, cowpox virus CrmD (O57079); T2, myxoma virus T2 (P29825); TNFRSF1B, human TNFRSF1B (P20333); TNFRSF1A, human TNFRSF1A (P19438).
Figure 4.
Figure 4. Hinge movements of CrmE and TNFRSF1A. (a) Superposition of monomers A and B from the crystal structure of CrmE. The two structurally conserved regions of CrmE, as identified by ESCET, are coloured maroon and yellow, respectively. The left-hand view shows the N-terminal structurally conserved regions of both monomers superposed and the right-hand view shows the C-terminal structurally conserved regions superposed. (b) Superposition of a representative set of human TNFRSF1A structures (PDB IDs 1tnr, 1ext and 1ncf). The two structurally conserved regions of TNFRSF1A, as identified by ESCET, are coloured tan and cyan, respectively. The left and right-hand views are as for (a). (c) Superposition of the structurally conserved regions of CrmE (maroon and yellow) and TNFRSF1A (tan and cyan); the C-terminal region is slightly offset for clarity. While the fold of the 50s loop (comprised primarily of the CRD2 A1 module) is conserved between CrmE and TNFRSF1A, the fold of the 90s loop (the CRD3 A2 module) differs significantly between these two proteins.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 372, 660-671) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19946139 K.Van Vliet, M.R.Mohamed, L.Zhang, N.Y.Villa, S.J.Werden, J.Liu, and G.McFadden (2009).
Poxvirus proteomics and virus-host protein interactions.
  Microbiol Mol Biol Rev, 73, 730-749.  
  19255488 Y.Mukai, T.Nakamura, Y.Yoshioka, S.Tsunoda, H.Kamada, S.Nakagawa, Y.Yamagata, and Y.Tsutsumi (2009).
Crystallization and preliminary X-ray analysis of the tumour necrosis factor alpha-tumour necrosis factor receptor type 2 complex.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 295-298.  
19838188 Z.Yang, A.P.West, and P.J.Bjorkman (2009).
Crystal structure of TNFalpha complexed with a poxvirus MHC-related TNF binding protein.
  Nat Struct Mol Biol, 16, 1189-1191.  
19008892 M.Krupovic, and D.H.Bamford (2008).
Virus evolution: how far does the double beta-barrel viral lineage extend?
  Nat Rev Microbiol, 6, 941-948.  
18704168 S.C.Graham, M.W.Bahar, S.Cooray, R.A.Chen, D.M.Whalen, N.G.Abrescia, D.Alderton, R.J.Owens, D.I.Stuart, G.L.Smith, and J.M.Grimes (2008).
Vaccinia virus proteins A52 and B14 Share a Bcl-2-like fold but have evolved to inhibit NF-kappaB rather than apoptosis.
  PLoS Pathog, 4, e1000128.
PDB codes: 2vvw 2vvx 2vvy
  18097093 T.S.Walter, E.J.Mancini, J.Kadlec, S.C.Graham, R.Assenberg, J.Ren, S.Sainsbury, R.J.Owens, D.I.Stuart, J.M.Grimes, and K.Harlos (2008).
Semi-automated microseeding of nanolitre crystallization experiments.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 14-18.  
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.