PDBsum entry 1rz7

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Immune system PDB id
Protein chains
211 a.a. *
219 a.a. *
GOL ×2
Waters ×240
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of human anti-HIV-1 gp120-reactive antibod
Structure: Fab 48d light chain. Chain: l. Engineered: yes. Fab 48d heavy chain. Chain: h. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: human herpesvirus 4. Expression_system_taxid: 10376. Expression_system_cell: immortalized b-cell clone fused wit murine b-cell fusion partner. Murine b-cell fusion partner
Biol. unit: Dimer (from PQS)
2.00Å     R-factor:   0.201     R-free:   0.231
Authors: C.C.Huang,M.Venturi,S.Majeed,M.J.Moore,S.Phogat,M.-Y.Zhang, D.S.Dimitrov,W.A.Hendrickson,J.Robinson,J.Sodroski,R.Wyatt, M.Farzan,P.D.Kwong
Key ref:
C.C.Huang et al. (2004). Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120. Proc Natl Acad Sci U S A, 101, 2706-2711. PubMed id: 14981267 DOI: 10.1073/pnas.0308527100
24-Dec-03     Release date:   03-Feb-04    
Go to PROCHECK summary

Protein chain
No UniProt id for this chain
Struc: 211 a.a.
Protein chain
No UniProt id for this chain
Struc: 219 a.a.
Key:    Secondary structure  CATH domain


DOI no: 10.1073/pnas.0308527100 Proc Natl Acad Sci U S A 101:2706-2711 (2004)
PubMed id: 14981267  
Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120.
C.C.Huang, M.Venturi, S.Majeed, M.J.Moore, S.Phogat, M.Y.Zhang, D.S.Dimitrov, W.A.Hendrickson, J.Robinson, J.Sodroski, R.Wyatt, H.Choe, M.Farzan, P.D.Kwong.
The conserved surface of the HIV-1 gp120 envelope glycoprotein that binds to the HIV-1 coreceptor is protected from humoral recognition by multiple layers of camouflage. Here we present sequence and genomic analyses for 12 antibodies that pierce these defenses and determine the crystal structures of 5. The data reveal mechanisms and atomic-level details for three unusual immune features: posttranslational mimicry of coreceptor by tyrosine sulfation of antibody, an alternative molecular mechanism controlling such sulfation, and highly selective V(H)-gene usage. When confronted by extraordinary viral defenses, the immune system unveils novel adaptive capabilities, with tyrosine sulfation enhancing the vocabulary of antigen recognition.
  Selected figure(s)  
Figure 1.
Fig. 1. Structure of the archetype CD4i antibody, 17b. (A) Complexed versus free structure of 17b. The Left two structures show the rerefined YU2 and HXBc2 ternary complexes after superposition of the 17b V[H] framework, with the two complexed Fab 17b in black C^ worm, interacting 17b side chains in green, the N-terminal domain of CD4 in yellow, and the molecular surface of YU2 core gp120 in red, except for the surface within 3.5 Å of 17b, which is blue. In this orientation, the viral membrane would be positioned toward the top of the page. The Right two structures show the two independent copies of free 17b from the P2[1]2[1]2[1] crystals superimposed on the complexed structures. The color and orientation for the complexed structures are the same as in Left, with the free 17b structures shown in blue with magenta interactive residues. The Far Right shows the entire Fab, including the constant portion. Whereas the variable domains are quite similar, considerable differences are seen in the constant portions, especially between the two free structures. (B) Details of gp120-17b interaction at CDR H2 and CDR H3. The electrostatic potential of gp120 is shown at the molecular surface colored blue for electropositive, red for acidic, and white for apolar. The Left two structures show 17b in the same orientation as A. The portion corresponding to the V[H] gene, VH1-69, has been colored green, except for residues altered by somatic mutation, which are colored magenta. The five side chains of the CDR H2 that interact with gp120 are shown: I52, I53, L54, V56, and H58. The Right two structures show an 90° view, adjusted so that the pseudo twofold axes of the Fab are aligned with the edges of the page. In this view, the acidic CDR H3 loop (yellow C^ worm) can be seen reaching up to contact a basic gp120 surface. Side chains of VH1-69 that interact with the CDR H3 loop are shown.
Figure 5.
Fig. 5. Atomic-level details of antibody sulfation. The sulfated tyrosine at position H100 of 412d is shown. Two of the five coordinating ligands (Lys-145 and Gln-147) are from the light chain of a symmetry-related molecule. Electron density (2F[o] - F[c]) is shown at 0.5 .
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22932267 D.Lingwood, P.M.McTamney, H.M.Yassine, J.R.Whittle, X.Guo, J.C.Boyington, C.J.Wei, and G.J.Nabel (2012).
Structural and genetic basis for development of broadly neutralizing influenza antibodies.
  Nature, 489, 566-570.
PDB code: 4evn
21479208 F.Breden, C.Lepik, N.S.Longo, M.Montero, P.E.Lipsky, and J.K.Scott (2011).
Comparison of antibody repertoires produced by HIV-1 infection, other chronic and acute infections, and systemic autoimmune disease.
  PLoS One, 6, e16857.  
  21465559 L.T.Da, J.M.Quan, and Y.D.Wu (2011).
Understanding the binding mode and function of BMS-488043 against HIV-1 viral entry.
  Proteins, 79, 1810-1819.  
21298133 R.A.Lerner (2011).
Rare antibodies from combinatorial libraries suggests an S.O.S. component of the human immunological repertoire.
  Mol Biosyst, 7, 1004-1012.  
21251008 T.Han, and W.A.Marasco (2011).
Structural basis of influenza virus neutralization.
  Ann N Y Acad Sci, 1217, 178-190.  
21088799 W.R.Liu, Y.S.Wang, and W.Wan (2011).
Synthesis of proteins with defined posttranslational modifications using the genetic noncanonical amino acid incorporation approach.
  Mol Biosyst, 7, 38-47.  
21161615 X.Shen, and G.D.Tomaras (2011).
Alterations of the B-cell response by HIV-1 replication.
  Curr HIV/AIDS Rep, 8, 23-30.  
20442740 B.F.Haynes, N.I.Nicely, and S.M.Alam (2010).
HIV-1 autoreactive antibodies: are they good or bad for HIV-1 prevention?
  Nat Struct Mol Biol, 17, 543-545.  
19824826 J.A.Hoxie (2010).
Toward an antibody-based HIV-1 vaccine.
  Annu Rev Med, 61, 135-152.  
20361049 J.O.Wrabl, and V.J.Hilser (2010).
Investigating homology between proteins using energetic profiles.
  PLoS Comput Biol, 6, e1000722.  
20660185 L.Kong, C.C.Huang, S.J.Coales, K.S.Molnar, J.Skinner, Y.Hamuro, and P.D.Kwong (2010).
Local conformational stability of HIV-1 gp120 in unliganded and CD4-bound states as defined by amide hydrogen/deuterium exchange.
  J Virol, 84, 10311-10321.  
20531016 M.D.Hicar, X.Chen, B.Briney, J.Hammonds, J.J.Wang, S.Kalams, P.W.Spearman, and J.E.Crowe (2010).
Pseudovirion particles bearing native HIV envelope trimers facilitate a novel method for generating human neutralizing monoclonal antibodies against HIV.
  J Acquir Immune Defic Syndr, 54, 223-235.  
20702640 M.Huber, K.M.Le, K.J.Doores, Z.Fulton, R.L.Stanfield, I.A.Wilson, and D.R.Burton (2010).
Very few substitutions in a germ line antibody are required to initiate significant domain exchange.
  J Virol, 84, 10700-10707.  
20080564 M.Pancera, S.Majeed, Y.E.Ban, L.Chen, C.C.Huang, L.Kong, Y.D.Kwon, J.Stuckey, T.Zhou, J.E.Robinson, W.R.Schief, J.Sodroski, R.Wyatt, and P.D.Kwong (2010).
Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility.
  Proc Natl Acad Sci U S A, 107, 1166-1171.
PDB codes: 3jwd 3jwo
  20923574 M.Wen, R.Arora, H.Wang, L.Liu, J.T.Kimata, and P.Zhou (2010).
GPI-anchored single chain Fv--an effective way to capture transiently-exposed neutralization epitopes on HIV-1 envelope spike.
  Retrovirology, 7, 79.  
20534513 R.Pejchal, L.M.Walker, R.L.Stanfield, S.K.Phogat, W.C.Koff, P.Poignard, D.R.Burton, and I.A.Wilson (2010).
Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1.
  Proc Natl Acad Sci U S A, 107, 11483-11488.
PDB codes: 3mug 3muh
20616231 T.Zhou, I.Georgiev, X.Wu, Z.Y.Yang, K.Dai, A.Finzi, Y.D.Kwon, J.F.Scheid, W.Shi, L.Xu, Y.Yang, J.Zhu, M.C.Nussenzweig, J.Sodroski, L.Shapiro, G.J.Nabel, J.R.Mascola, and P.D.Kwong (2010).
Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01.
  Science, 329, 811-817.
PDB code: 3ngb
19251591 D.C.Ekiert, G.Bhabha, M.A.Elsliger, R.H.Friesen, M.Jongeneelen, M.Throsby, J.Goudsmit, and I.A.Wilson (2009).
Antibody recognition of a highly conserved influenza virus epitope.
  Science, 324, 246-251.
PDB codes: 3gbm 3gbn
19287373 J.F.Scheid, H.Mouquet, N.Feldhahn, M.S.Seaman, K.Velinzon, J.Pietzsch, R.G.Ott, R.M.Anthony, H.Zebroski, A.Hurley, A.Phogat, B.Chakrabarti, Y.Li, M.Connors, F.Pereyra, B.D.Walker, H.Wardemann, D.Ho, R.T.Wyatt, J.R.Mascola, J.V.Ravetch, and M.C.Nussenzweig (2009).
Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals.
  Nature, 458, 636-640.  
19234466 J.Sui, W.C.Hwang, S.Perez, G.Wei, D.Aird, L.M.Chen, E.Santelli, B.Stec, G.Cadwell, M.Ali, H.Wan, A.Murakami, A.Yammanuru, T.Han, N.J.Cox, L.A.Bankston, R.O.Donis, R.C.Liddington, and W.A.Marasco (2009).
Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses.
  Nat Struct Mol Biol, 16, 265-273.
PDB code: 3fku
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.  
19448659 P.D.Kwong, and I.A.Wilson (2009).
HIV-1 and influenza antibodies: seeing antigens in new ways.
  Nat Immunol, 10, 573-578.  
19234464 T.T.Wang, and P.Palese (2009).
Universal epitopes of influenza virus hemagglutinins?
  Nat Struct Mol Biol, 16, 233-234.  
19748484 X.Xiao, W.Chen, Y.Feng, Z.Zhu, P.Prabakaran, Y.Wang, M.Y.Zhang, N.S.Longo, and D.S.Dimitrov (2009).
Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: implications for evasion of immune responses and design of vaccine immunogens.
  Biochem Biophys Res Commun, 390, 404-409.  
19225108 Y.Guan, M.M.Sajadi, R.Kamin-Lewis, T.R.Fouts, A.Dimitrov, Z.Zhang, R.R.Redfield, A.L.DeVico, R.C.Gallo, and G.K.Lewis (2009).
Discordant memory B cell and circulating anti-Env antibody responses in HIV-1 infection.
  Proc Natl Acad Sci U S A, 106, 3952-3957.  
19004942 Y.Li, K.Svehla, M.K.Louder, D.Wycuff, S.Phogat, M.Tang, S.A.Migueles, X.Wu, A.Phogat, G.M.Shaw, M.Connors, J.Hoxie, J.R.Mascola, and R.Wyatt (2009).
Analysis of neutralization specificities in polyclonal sera derived from human immunodeficiency virus type 1-infected individuals.
  J Virol, 83, 1045-1059.  
18413603 A.K.Kashyap, J.Steel, A.F.Oner, M.A.Dillon, R.E.Swale, K.M.Wall, K.J.Perry, A.Faynboym, M.Ilhan, M.Horowitz, L.Horowitz, P.Palese, R.R.Bhatt, and R.A.Lerner (2008).
Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategies.
  Proc Natl Acad Sci U S A, 105, 5986-5991.  
19004806 C.C.Liu, A.V.Mack, M.L.Tsao, J.H.Mills, H.S.Lee, H.Choe, M.Farzan, P.G.Schultz, and V.V.Smider (2008).
Protein evolution with an expanded genetic code.
  Proc Natl Acad Sci U S A, 105, 17688-17693.  
17680702 C.Seibert, and T.P.Sakmar (2008).
Toward a framework for sulfoproteomics: Synthesis and characterization of sulfotyrosine-containing peptides.
  Biopolymers, 90, 459-477.  
18218997 J.Liu, S.Louie, W.Hsu, K.M.Yu, H.B.Nicholas, and G.L.Rosenquist (2008).
Tyrosine sulfation is prevalent in human chemokine receptors important in lung disease.
  Am J Respir Cell Mol Biol, 38, 738-743.  
19079604 M.Throsby, E.van den Brink, M.Jongeneelen, L.L.Poon, P.Alard, L.Cornelissen, A.Bakker, F.Cox, E.van Deventer, Y.Guan, J.Cinatl, J.ter Meulen, I.Lasters, R.Carsetti, M.Peiris, Kruif, and J.Goudsmit (2008).
Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM+ memory B cells.
  PLoS ONE, 3, e3942.  
18784843 R.Taube, Q.Zhu, C.Xu, F.Diaz-Griffero, J.Sui, E.Kamau, M.Dwyer, D.Aird, and W.A.Marasco (2008).
Lentivirus display: stable expression of human antibodies on the surface of human cells and virus particles.
  PLoS ONE, 3, e3181.  
18957538 W.Chen, Z.Zhu, Y.Feng, and D.S.Dimitrov (2008).
Human domain antibodies to conserved sterically restricted regions on gp120 as exceptionally potent cross-reactive HIV-1 neutralizers.
  Proc Natl Acad Sci U S A, 105, 17121-17126.  
17901336 C.C.Huang, S.N.Lam, P.Acharya, M.Tang, S.H.Xiang, S.S.Hussan, R.L.Stanfield, J.Robinson, J.Sodroski, I.A.Wilson, R.Wyatt, C.A.Bewley, and P.D.Kwong (2007).
Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4.
  Science, 317, 1930-1934.
PDB codes: 2qad 2rll
17335583 C.H.Tung, J.W.Huang, and J.M.Yang (2007).
Kappa-alpha plot derived structural alphabet and BLOSUM-like substitution matrix for rapid search of protein structure database.
  Genome Biol, 8, R31.  
17910770 J.V.Ponomarenko, and P.E.Bourne (2007).
Antibody-protein interactions: benchmark datasets and prediction tools evaluation.
  BMC Struct Biol, 7, 64.  
16933990 G.Zanetti, J.A.Briggs, K.Grünewald, Q.J.Sattentau, and S.D.Fuller (2006).
Cryo-electron tomographic structure of an immunodeficiency virus envelope complex in situ.
  PLoS Pathog, 2, e83.  
16862157 M.A.Luftig, M.Mattu, P.Di Giovine, R.Geleziunas, R.Hrin, G.Barbato, E.Bianchi, M.D.Miller, A.Pessi, and A.Carfí (2006).
Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody.
  Nat Struct Mol Biol, 13, 740-747.
PDB code: 2cmr
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.  
16610981 V.Choudhry, M.Y.Zhang, D.Dimitrova, P.Prabakaran, A.S.Dimitrov, T.R.Fouts, and D.S.Dimitrov (2006).
Antibody-based inhibitors of HIV infection.
  Expert Opin Biol Ther, 6, 523-531.  
16904645 V.Choudhry, M.Y.Zhang, I.Harris, I.A.Sidorov, B.Vu, A.S.Dimitrov, T.Fouts, and D.S.Dimitrov (2006).
Increased efficacy of HIV-1 neutralization by antibodies at low CCR5 surface concentration.
  Biochem Biophys Res Commun, 348, 1107-1115.  
16219699 D.R.Burton, R.L.Stanfield, and I.A.Wilson (2005).
Antibody vs. HIV in a clash of evolutionary titans.
  Proc Natl Acad Sci U S A, 102, 14943-14948.  
15867093 J.M.Decker, F.Bibollet-Ruche, X.Wei, S.Wang, D.N.Levy, W.Wang, E.Delaporte, M.Peeters, C.A.Derdeyn, S.Allen, E.Hunter, M.S.Saag, J.A.Hoxie, B.H.Hahn, P.D.Kwong, J.E.Robinson, and G.M.Shaw (2005).
Antigenic conservation and immunogenicity of the HIV coreceptor binding site.
  J Exp Med, 201, 1407-1419.  
16189008 R.A.Wilkinson, C.Piscitelli, M.Teintze, L.A.Cavacini, M.R.Posner, and C.M.Lawrence (2005).
Structure of the Fab fragment of F105, a broadly reactive anti-human immunodeficiency virus (HIV) antibody that recognizes the CD4 binding site of HIV type 1 gp120.
  J Virol, 79, 13060-13069.
PDB code: 1u6a
15857992 S.H.Xiang, M.Farzan, Z.Si, N.Madani, L.Wang, E.Rosenberg, J.Robinson, and J.Sodroski (2005).
Functional mimicry of a human immunodeficiency virus type 1 coreceptor by a neutralizing monoclonal antibody.
  J Virol, 79, 6068-6077.  
16195378 T.Zhou, D.H.Hamer, W.A.Hendrickson, Q.J.Sattentau, and P.D.Kwong (2005).
Interfacial metal and antibody recognition.
  Proc Natl Acad Sci U S A, 102, 14575-14580.
PDB codes: 2adg 2adi 2adj
15219551 D.A.Garber, G.Silvestri, and M.B.Feinberg (2004).
Prospects for an AIDS vaccine: three big questions, no easy answers.
  Lancet Infect Dis, 4, 397-413.  
15367639 G.Ofek, M.Tang, A.Sambor, H.Katinger, J.R.Mascola, R.Wyatt, and P.D.Kwong (2004).
Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope.
  J Virol, 78, 10724-10737.
PDB codes: 1tjg 1tjh 1tji
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.