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Viral protein PDB id
1nj0
Jmol
Contents
Protein chain
16 a.a.
PDB id:
1nj0
Name: Viral protein
Title: Nmr structure of a v3 (mn isolate) peptide bound to 447-52d, a human HIV-1 neutralizing antibody
Structure: Exterior membrane glycoprotein(gp120). Chain: a. Fragment: v3 loop (residues 309-324). Engineered: yes
Source: Human immunodeficiency virus 1. Organism_taxid: 11676. Gene: env. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 29 models
Authors: M.Sharon,N.Kessler,R.Levy,S.Zolla-Pazner,M.Gorlach, J.Anglister
Key ref:
M.Sharon et al. (2003). Alternative conformations of HIV-1 V3 loops mimic beta hairpins in chemokines, suggesting a mechanism for coreceptor selectivity. Structure, 11, 225-236. PubMed id: 12575942 DOI: 10.1016/S0969-2126(03)00011-X
Date:
30-Dec-02     Release date:   25-Feb-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05877  (ENV_HV1MN) -  Envelope glycoprotein gp160
Seq:
Struc: 		 
Seq:
Struc: 		856 a.a.
16 a.a.
Key:    PfamA domain  Secondary structure

 

 
DOI no: 10.1016/S0969-2126(03)00011-X Structure 11:225-236 (2003)
PubMed id: 12575942  
 
 
Alternative conformations of HIV-1 V3 loops mimic beta hairpins in chemokines, suggesting a mechanism for coreceptor selectivity.
M.Sharon, N.Kessler, R.Levy, S.Zolla-Pazner, M.Görlach, J.Anglister.
 
  ABSTRACT  
 
The V3 loop of the HIV-1 envelope glycoprotein gp120 is involved in binding to the CCR5 and CXCR4 coreceptors. The structure of an HIV-1(MN) V3 peptide bound to the Fv of the broadly neutralizing human monoclonal antibody 447-52D was solved by NMR and found to be a beta hairpin. This structure of V3(MN) was found to have conformation and sequence similarities to beta hairpins in CD8 and CCR5 ligands MIP-1alpha, MIP-1beta, and RANTES and differed from the beta hairpin of a V3(IIIB) peptide bound to the strain-specific murine anti-gp120(IIIB) antibody 0.5beta. In contrast to the structure of the bound V3(MN) peptide, the V3(IIIB) peptide resembles a beta hairpin in SDF-1, a CXCR4 ligand. These data suggest that the 447-52D-bound V3(MN) and the 0.5beta-bound V3(IIIB) structures represent alternative V3 conformations responsible for selective interactions with CCR5 and CXCR4, respectively.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. The Solution Structure of the V3[MN] Epitope (312-327gp120[MN]) Bound to the 447 Fv(A) Backbone superposition of 29 lowest-energy structures.(B) A ribbon diagram of the energy-minimized average structure; the terminal residues of the b strands are numbered.(C) A stereo representation of V3[MN] bound to the 447 Fv showing side chain interactions and hydrogen bonds within the peptide (red). Side chains pointing out from the page, yellow; side chains pointing inward, green.
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 225-236) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21281498 M.J.Bolton, and R.F.Garry (2011).
Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines.
  Virol J, 8, 45.  
21264298 O.Chertov, N.Zhang, X.Chen, J.J.Oppenheim, J.Lubkowski, C.McGrath, R.C.Sowder, B.J.Crise, A.Malyguine, M.A.Kutzler, A.D.Steele, E.E.Henderson, and T.J.Rogers (2011).
Novel peptides based on HIV-1 gp120 sequence with homology to chemokines inhibit HIV infection in cell culture.
  PLoS One, 6, e14474.  
20421997 C.E.Hioe, T.Wrin, M.S.Seaman, X.Yu, B.Wood, S.Self, C.Williams, M.K.Gorny, and S.Zolla-Pazner (2010).
Anti-V3 monoclonal antibodies display broad neutralizing activities against multiple HIV-1 subtypes.
  PLoS One, 5, e10254.  
20845361 M.Hertje, M.Zhou, and U.Dietrich (2010).
Inhibition of HIV-1 entry: multiple keys to close the door.
  ChemMedChem, 5, 1825-1835.  
20923564 M.Masso, and I.I.Vaisman (2010).
Accurate and efficient gp120 V3 loop structure based models for the determination of HIV-1 co-receptor usage.
  BMC Bioinformatics, 11, 494.  
20577269 S.Zolla-Pazner, and T.Cardozo (2010).
Structure-function relationships of HIV-1 envelope sequence-variable regions refocus vaccine design.
  Nat Rev Immunol, 10, 527-535.  
20622876 X.Jiang, V.Burke, M.Totrov, C.Williams, T.Cardozo, M.K.Gorny, S.Zolla-Pazner, and X.P.Kong (2010).
Conserved structural elements in the V3 crown of HIV-1 gp120.
  Nat Struct Mol Biol, 17, 955-961.
PDB codes: 3go1 3mlr 3mls 3mlt 3mlu 3mlv 3mlw 3mlx 3mly 3mlz
19103601 A.Mascioni, B.E.Bentley, R.Camarda, D.A.Dilts, P.Fink, V.Gusarova, S.K.Hoiseth, J.Jacob, S.L.Lin, K.Malakian, L.K.McNeil, T.Mininni, F.Moy, E.Murphy, E.Novikova, S.Sigethy, Y.Wen, G.W.Zlotnick, and D.H.Tsao (2009).
Structural Basis for the Immunogenic Properties of the Meningococcal Vaccine Candidate LP2086.
  J Biol Chem, 284, 8738-8746.
PDB code: 2kdy
19281264 A.Mor, E.Segal, B.Mester, B.Arshava, O.Rosen, F.X.Ding, J.Russo, A.Dafni, F.Schvartzman, T.Scherf, F.Naider, and J.Anglister (2009).
Mimicking the structure of the V3 epitope bound to HIV-1 neutralizing antibodies.
  Biochemistry, 48, 3288-3303.  
18952295 M.K.Gorny, X.H.Wang, C.Williams, B.Volsky, K.Revesz, B.Witover, S.Burda, M.Urbanski, P.Nyambi, C.Krachmarov, A.Pinter, S.Zolla-Pazner, and A.Nadas (2009).
Preferential use of the VH5-51 gene segment by the human immune response to code for antibodies against the V3 domain of HIV-1.
  Mol Immunol, 46, 917-926.  
19117029 P.A.Galanakis, N.G.Kandias, A.K.Rizos, D.Morikis, E.Krambovitis, and G.A.Spyroulias (2009).
NMR evidence of charge-dependent interaction between various PND V3 and CCR5 N-terminal peptides.
  Biopolymers, 92, 94.  
19815247 S.X.Du, R.J.Idiart, E.B.Mariano, H.Chen, P.Jiang, L.Xu, K.M.Ostrow, T.Wrin, P.Phung, J.M.Binley, C.J.Petropoulos, J.A.Ballantyne, and R.G.Whalen (2009).
Effect of trimerization motifs on quaternary structure, antigenicity, and immunogenicity of a noncleavable HIV-1 gp140 envelope glycoprotein.
  Virology, 395, 33-44.  
19913488 V.Burke, C.Williams, M.Sukumaran, S.S.Kim, H.Li, X.H.Wang, M.K.Gorny, S.Zolla-Pazner, and X.P.Kong (2009).
Structural basis of the cross-reactivity of genetically related human anti-HIV-1 mAbs: implications for design of V3-based immunogens.
  Structure, 17, 1538-1546.
PDB codes: 3ghb 3ghe
18566514 A.K.Dhillon, R.L.Stanfield, M.K.Gorny, C.Williams, S.Zolla-Pazner, and I.A.Wilson (2008).
Structure determination of an anti-HIV-1 Fab 447-52D-peptide complex from an epitaxially twinned data set.
  Acta Crystallogr D Biol Crystallogr, 64, 792-802.
PDB code: 3c2a
18345927 A.Verma, and W.Wenzel (2008).
Conformational landscape of the HIV-V3 hairpin loop from all-atom free-energy simulations.
  J Chem Phys, 128, 105103.  
18366016 D.Katagiri, H.Fuji, S.Neya, and T.Hoshino (2008).
Ab initio protein structure prediction with force field parameters derived from water-phase quantum chemical calculation.
  J Comput Chem, 29, 1930-1944.  
18815292 J.M.Binley, E.A.Lybarger, E.T.Crooks, M.S.Seaman, E.Gray, K.L.Davis, J.M.Decker, D.Wycuff, L.Harris, N.Hawkins, B.Wood, C.Nathe, D.Richman, G.D.Tomaras, F.Bibollet-Ruche, J.E.Robinson, L.Morris, G.M.Shaw, D.C.Montefiori, and J.R.Mascola (2008).
Profiling the specificity of neutralizing antibodies in a large panel of plasmas from patients chronically infected with human immunodeficiency virus type 1 subtypes B and C.
  J Virol, 82, 11651-11668.  
18003735 M.B.Patel, N.G.Hoffman, and R.Swanstrom (2008).
Subtype-specific conformational differences within the V3 region of subtype B and subtype C human immunodeficiency virus type 1 Env proteins.
  J Virol, 82, 903-916.  
18818125 M.Cadogan, and A.G.Dalgleish (2008).
HIV immunopathogenesis and strategies for intervention.
  Lancet Infect Dis, 8, 675-684.  
18544021 M.Cadogan, B.Austen, J.L.Heeney, and A.G.Dalgleish (2008).
HLA homology within the C5 domain promotes peptide binding by HIV type 1 gp120.
  AIDS Res Hum Retroviruses, 24, 845-855.  
19081789 M.Humbert, R.A.Rasmussen, H.Ong, F.M.Kaiser, S.L.Hu, and R.M.Ruprecht (2008).
Inducing cross-clade neutralizing antibodies against HIV-1 by immunofocusing.
  PLoS ONE, 3, e3937.  
18275085 O.Rosen, A.O.Samson, and J.Anglister (2008).
Correlated mutations at gp120 positions 322 and 440: implications for gp120 structure.
  Proteins, 71, 1066-1070.  
17954689 W.Lai, L.Huang, P.Ho, Z.Li, D.Montefiori, and C.H.Chen (2008).
Betulinic Acid Derivatives That Target gp120 and Inhibit Multiple Genetic Subtypes of Human Immunodeficiency Virus Type 1.
  Antimicrob Agents Chemother, 52, 128-136.  
17510784 L.Luo, Y.Li, S.D.Ha, and C.Y.Kang (2007).
Hydrophilicity dependent budding and secretion of chimeric HIV Gag-V3 virus-like particles.
  Virus Genes, 35, 187-193.  
17397254 O.Sander, T.Sing, I.Sommer, A.J.Low, P.K.Cheung, P.R.Harrigan, T.Lengauer, and F.S.Domingues (2007).
Structural descriptors of gp120 V3 loop for the prediction of HIV-1 coreceptor usage.
  PLoS Comput Biol, 3, e58.  
17418361 R.Pantophlet, R.O.Aguilar-Sino, T.Wrin, L.A.Cavacini, and D.R.Burton (2007).
Analysis of the neutralization breadth of the anti-V3 antibody F425-B4e8 and re-assessment of its epitope fine specificity by scanning mutagenesis.
  Virology, 364, 441-453.  
17131136 S.Q.Liu, S.X.Liu, and Y.X.Fu (2007).
Dynamic domains and geometrical properties of HIV-1 gp120 during conformational changes induced by CD4 binding.
  J Mol Model, 13, 411-424.  
17411375 T.Cardozo, T.Kimura, S.Philpott, B.Weiser, H.Burger, and S.Zolla-Pazner (2007).
Structural basis for coreceptor selectivity by the HIV type 1 V3 loop.
  AIDS Res Hum Retroviruses, 23, 415-426.  
16978155 A.M.Andrianov, and V.G.Veresov (2006).
Determination of structurally conservative amino acids of the HIV-1 protein gp120 V3 loop as promising targets for drug design by protein engineering approaches.
  Biochemistry (Mosc), 71, 906-914.  
16315040 J.K.Weltman, G.Skowron, and G.B.Loriot (2006).
HIV-1 GP120 V3 conformational and informational entropies.
  J Mol Model, 12, 362-365.  
16809292 M.K.Gorny, C.Williams, B.Volsky, K.Revesz, X.H.Wang, S.Burda, T.Kimura, F.A.Konings, A.Nádas, C.A.Anyangwe, P.Nyambi, C.Krachmarov, A.Pinter, and S.Zolla-Pazner (2006).
Cross-clade neutralizing activity of human anti-V3 monoclonal antibodies derived from the cells of individuals infected with non-B clades of human immunodeficiency virus type 1.
  J Virol, 80, 6865-6872.  
16731948 R.L.Stanfield, M.K.Gorny, S.Zolla-Pazner, and I.A.Wilson (2006).
Crystal structures of human immunodeficiency virus type 1 (HIV-1) neutralizing antibody 2219 in complex with three different V3 peptides reveal a new binding mode for HIV-1 cross-reactivity.
  J Virol, 80, 6093-6105.
PDB codes: 2b0s 2b1a 2b1h
16361230 T.Watabe, H.Kishino, Y.Okuhara, and Y.Kitazoe (2006).
Fold recognition of the human immunodeficiency virus type 1 V3 loop and flexibility of its crown structure during the course of adaptation to a host.
  Genetics, 172, 1385-1396.  
16157597 A.de Parseval, M.D.Bobardt, A.Chatterji, U.Chatterji, J.H.Elder, G.David, S.Zolla-Pazner, M.Farzan, T.H.Lee, and P.A.Gallay (2005).
A highly conserved arginine in gp120 governs HIV-1 binding to both syndecans and CCR5 via sulfated motifs.
  J Biol Chem, 280, 39493-39504.  
  16720980 E.T.Crooks, P.L.Moore, D.Richman, J.Robinson, J.A.Crooks, M.Franti, N.Schülke, and J.M.Binley (2005).
Characterizing anti-HIV monoclonal antibodies and immune sera by defining the mechanism of neutralization.
  Hum Antibodies, 14, 101-113.  
15725757 O.Hartley, P.J.Klasse, Q.J.Sattentau, and J.P.Moore (2005).
V3: HIV's switch-hitter.
  AIDS Res Hum Retroviruses, 21, 171-189.  
15890935 P.Lusso, P.L.Earl, F.Sironi, F.Santoro, C.Ripamonti, G.Scarlatti, R.Longhi, E.A.Berger, and S.E.Burastero (2005).
Cryptic nature of a conserved, CD4-inducible V3 loop neutralization epitope in the native envelope glycoprotein oligomer of CCR5-restricted, but not CXCR4-using, primary human immunodeficiency virus type 1 strains.
  J Virol, 79, 6957-6968.  
15047829 E.Billick, C.Seibert, P.Pugach, T.Ketas, A.Trkola, M.J.Endres, N.J.Murgolo, E.Coates, G.R.Reyes, B.M.Baroudy, T.P.Sakmar, J.P.Moore, and S.E.Kuhmann (2004).
The differential sensitivity of human and rhesus macaque CCR5 to small-molecule inhibitors of human immunodeficiency virus type 1 entry is explained by a single amino acid difference and suggests a mechanism of action for these inhibitors.
  J Virol, 78, 4134-4144.  
15285704 I.K.Srivastava, J.B.Ulmer, and S.W.Barnett (2004).
Neutralizing antibody responses to HIV: role in protective immunity and challenges for vaccine design.
  Expert Rev Vaccines, 3, S33-S52.  
  15314679 J.A.Berzofsky, J.D.Ahlers, J.Janik, J.Morris, S.Oh, M.Terabe, and I.M.Belyakov (2004).
Progress on new vaccine strategies against chronic viral infections.
  J Clin Invest, 114, 450-462.  
15597205 J.K.Weltman, G.Skowron, and G.B.Loriot (2004).
The HF-SCF energy of HIV-1 MNgp120 V3 hairpin loop conformers.
  J Mol Model, 10, 367-372.  
15285705 J.L.Heeney (2004).
Requirement of diverse T-helper responses elicited by HIV vaccines: induction of highly targeted humoral and CTL responses.
  Expert Rev Vaccines, 3, S53-S64.  
15542675 J.M.Binley, T.Wrin, B.Korber, M.B.Zwick, M.Wang, C.Chappey, G.Stiegler, R.Kunert, S.Zolla-Pazner, H.Katinger, C.J.Petropoulos, and D.R.Burton (2004).
Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies.
  J Virol, 78, 13232-13252.  
15285710 N.V.Malkevitch, and M.Robert-Guroff (2004).
A call for replicating vector prime-protein boost strategies in HIV vaccine design.
  Expert Rev Vaccines, 3, S105-S117.  
15016849 R.A.McCaffrey, C.Saunders, M.Hensel, and L.Stamatatos (2004).
N-linked glycosylation of the V3 loop and the immunologically silent face of gp120 protects human immunodeficiency virus type 1 SF162 from neutralization by anti-gp120 and anti-gp41 antibodies.
  J Virol, 78, 3279-3295.  
14962380 R.L.Stanfield, M.K.Gorny, C.Williams, S.Zolla-Pazner, and I.A.Wilson (2004).
Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52D.
  Structure, 12, 193-204.
PDB code: 1q1j
15016843 S.Pöhlmann, C.Davis, S.Meister, G.J.Leslie, C.Otto, J.D.Reeves, B.A.Puffer, A.Papkalla, M.Krumbiegel, A.Marzi, S.Lorenz, J.Münch, R.W.Doms, and F.Kirchhoff (2004).
Amino acid 324 in the simian immunodeficiency virus SIVmac V3 loop can confer CD4 independence and modulate the interaction with CCR5 and alternative coreceptors.
  J Virol, 78, 3223-3232.  
15103622 S.T.Hsu, and A.M.Bonvin (2004).
Atomic insight into the CD4 binding-induced conformational changes in HIV-1 gp120.
  Proteins, 55, 582-593.  
15039757 S.Zolla-Pazner (2004).
Identifying epitopes of HIV-1 that induce protective antibodies.
  Nat Rev Immunol, 4, 199-210.  
15588347 S.Zolla-Pazner, P.Zhong, K.Revesz, B.Volsky, C.Williams, P.Nyambi, and M.K.Gorny (2004).
The cross-clade neutralizing activity of a human monoclonal antibody is determined by the GPGR V3 motif of HIV type 1.
  AIDS Res Hum Retroviruses, 20, 1254-1258.  
15242536 Z.Wu, E.Golub, W.R.Abrams, and D.Malamud (2004).
gp340 (SAG) binds to the V3 sequence of gp120 important for chemokine receptor interaction.
  AIDS Res Hum Retroviruses, 20, 600-607.  
12887913 G.Lin, and J.A.Hoxie (2003).
CCR5 mimicry by sulfated human anti-HIV-1 antibodies.
  Cell, 114, 147-148.  
15080183 S.A.Calarota, and D.B.Weiner (2003).
Present status of human HIV vaccine development.
  AIDS, 17, S73-S84.  
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.