PDBsum entry 1hhv

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Viral protein PDB id
Protein chain
74 a.a. *
* Residue conservation analysis
PDB id:
Name: Viral protein
Title: Solution structure of virus chemokine vmip-ii
Structure: Virus chemokine vmip-ii. Chain: a. Synonym: orf k4. Vmip-ii. Macrophage inflammatory protein 1-alpha homolog. Engineered: yes
Source: Synthetic: yes. Other_details: sequence from human herpesvirus 8
NMR struc: 25 models
Authors: W.Shao,E.Fernandez,J.M.Navenot,J.Wilken,D.A.Thompson, S.Pepiper,B.I.Schweitzer,E.Lolis
Key ref:
W.Shao et al. (2001). CCR2 and CCR5 receptor-binding properties of herpesvirus-8 vMIP-II based on sequence analysis and its solution structure. Eur J Biochem, 268, 2948-2959. PubMed id: 11358512 DOI: 10.1046/j.1432-1327.2001.02184.x
06-Dec-98     Release date:   16-Sep-03    
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Protein chain
Pfam   ArchSchema ?
Q98157  (VMI2_HHV8P) -  Viral macrophage inflammatory protein 2
94 a.a.
74 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     cell chemotaxis   1 term 
  Biochemical function     cytokine activity     1 term  


DOI no: 10.1046/j.1432-1327.2001.02184.x Eur J Biochem 268:2948-2959 (2001)
PubMed id: 11358512  
CCR2 and CCR5 receptor-binding properties of herpesvirus-8 vMIP-II based on sequence analysis and its solution structure.
W.Shao, E.Fernandez, A.Sachpatzidis, J.Wilken, D.A.Thompson, B.I.Schweitzer, E.Lolis.
Human herpesvirus-8 (HHV-8) is the infectious agent responsible for Kaposi's sarcoma and encodes a protein, macrophage inflammatory protein-II (vMIP-II), which shows sequence similarity to the human CC chemokines. vMIP-II has broad receptor specificity that crosses chemokine receptor subfamilies, and inhibits HIV-1 viral entry mediated by numerous chemokine receptors. In this study, the solution structure of chemically synthesized vMIP-II was determined by nuclear magnetic resonance. The protein is a monomer and possesses the chemokine fold consisting of a flexible N-terminus, three antiparallel beta strands, and a C-terminal alpha helix. Except for the N-terminal residues (residues 1-13) and the last two C-terminal residues (residues 73-74), the structure of vMIP-II is well-defined, exhibiting average rmsd of 0.35 and 0.90 A for the backbone heavy atoms and all heavy atoms of residues 14-72, respectively. Taking into account the sequence differences between the various CC chemokines and comparing their three-dimensional structures allows us to implicate residues that influence the quaternary structure and receptor binding and activation of these proteins in solution. The analysis of the sequence and three-dimensional structure of vMIP-II indicates the presence of epitopes involved in binding two receptors CCR2 and CCR5. We propose that vMIP-II was initially specific for CCR5 and acquired receptor-binding properties to CCR2 and other chemokine receptors.
  Selected figure(s)  
Figure 1.
Fig. 1. (A) ^1H NMR spectrum of vMIP-II at pH 3.25, 5.10, and 7.00, and (B) determination of the self-diffusion coefficients (Ds) of vMIP-II at pH 3.25 and 7.0. (A) Indicates that the overall three-dimensional structure of vMIP-II is similar at all three pH values (B) Triangles: vMIP-II at pH 3.25; circles: vMIP-II at pH 7.0.
Figure 4.
Fig. 4. Sequence and structural analysis of receptor binding specificities for CCR2 and CCR5. (A) Multiple sequence alignment of vMIP-II, CCR2-activating chemokines (MCP-1, MCP-2, MCP-3, and MCP-4) and CCR5-activating chemokines (MIP-1 , MIP-1 , RANTES, and MCP-2). To eliminate complications due to MCP-2, which activates CCR2 and CCR5, this chemokine is omitted from the analysis. Invariant residues within each group of chemokines are shown in bold. A restricted set of unique, invariant residues that may be involved in receptor selectivity are shown in green (CCR2-activating chemokines) and red (CCR5-activating chemokines). To arrive at this restricted set of invariant residues, amino acids with the following criteria were omitted: (a) residues that were invariant among all CC chemokines (VMIP-II interacts with the CC chemokine receptors CCR1, CCR2, CCR3 and CCR5. Chemokines that interact with at least one of these receptors include MCP-1, MCP-2, MCP-3, MCP-4, MIP-1 , MIP-1 , RANTES, eotaxin-1, and MPIF-2.) with which vMIP-II shares receptor binding (underlined in the MCP-2, eotaxin-1, and MPIF-2 sequences), or (b) invariant residues within one group of chemokines (CCR2- or CCR5-activating chemokines) that are also present in at least one chemokine from the other group of chemokines. The restricted invariant residues from each set of chemokines that are present in vMIP-II are shown in the same color scheme. (B) Ribbon diagram of MCP-1, vMIP-II, and RANTES. The solvent-accessible surface of the restricted set of invariant residues for CCR2- and CCR5-activating chemokines are shown in green and red, respectively. The solvent-accessible surface of the invariant residues from both CCR5- and CCR2-activating residues that are present in vMIP-II is shown in the context of the ribbon structure of vMIP-II with the same color scheme as above.
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2001, 268, 2948-2959) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
15039444 V.Petkovic, C.Moghini, S.Paoletti, M.Uguccioni, and B.Gerber (2004).
Eotaxin-3/CCL26 is a natural antagonist for CC chemokine receptors 1 and 5. A human chemokine with a regulatory role.
  J Biol Chem, 279, 23357-23363.  
11807180 E.J.Fernandez, and E.Lolis (2002).
Structure, function, and inhibition of chemokines.
  Annu Rev Pharmacol Toxicol, 42, 469-499.  
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