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 2rll
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SER-PRO-ILE-TYS-
ASP-ILE-ASN-TYS-
TYR
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PDB id: 2rll
Name: Membrane protein
Title: Ccr5 nt(7-15)

Structure:		 9-mer from c-c chemokine receptor type 5. Chain: a. Fragment: extracellular domain, unp residues 7-15. Synonym: c-c ckr-5, cc-ckr-5, ccr-5, ccr5, HIV-1 fusion coreceptor, chemr13, cd195 antigen. Engineered: yes

Source: 		Synthetic: yes. Other_details: this peptide was chemically synthesized by solid phase synthesis and purified by reverse phase hplc.. This sequence occurs naturally in humans.

UniProt:
() Pfam  

Resolution: 		not givenÅ

NMR structure: 		1 models

Authors: 		C.A.Bewley,S.N.Lam

Key ref:
C.C.Huang et al. (2007). Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4.. Science, 317, 1930-1934. [PubMed id: 17901336] [DOI: 10.1126/science.1145373]

Date: 		21-Jul-07

Release date: 		25-Sep-07
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    Key reference    
 
 
DOI no: 10.1126/science.1145373 Science 317:1930-1934 (2007)
PubMed id: 17901336  
 
 
Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4.
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, P.D.Kwong.
 
  ABSTRACT  
 
The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (alpha-helix) and 412d (extended loop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Structure of the tyrosine-sulfated antibody 412d in complex with HIV-1 gp120 and CD4. (A) Ribbon representation. CD4 is yellow, the heavy chain of Fab 412d is dark blue, the light chain is cyan, and gp120 is gray, except for the V3 loop, which is orange. The CDR H3 loop of 412d is red, with sulfotyrosines depicted in stick representation. (B) Close-up, with molecular surface of gp120 in gray and sulfotyrosines of 412d (red labels) and select residues of gp120 (black labels) in stick representation. Dotted lines represent coordinating hydrogen bonds between gp120 and the sulfate group of Tys100c^412d. The sulfate of Tys 100c^412d makes a full complement of ionic interactions: a salt bridge to Arg 298^gp120 and hydrogen bonds to the side-chain nitrogen of Asn 302^gp120, the side-chain hydroxyl of Thr 303^gp120, and the main-chain amides of 302^gp120, 303^gp120, and 441^gp120 (34). 		Figure 4.
Fig. 4. A conserved site for binding sulfotyrosine on HIV-1 gp120. (A) Alterations of the V3 base to accommodate binding of sulfotyrosine. The gp120 (gray) region around the V3 loop (orange) is illustrated in ribbon diagram, with an overlying semitransparent surface for unbound (left panel) and bound (right panel) conformations. Binding of the CCR5 N terminus (purple) or the 412d CDR H3 (red), each with two sulfotyrosines (stick representation, with red and purple labels), alters the V3 base, forming a sulfotyrosine binding pocket and a rigid ß-hairpin. (B) Close-up of the conserved sulfotyrosine binding pocket. The orientation shown is similar to that in Figs. 2B and 3B [ 90° from (A) about a diagonal axis, as defined by the long axis of the V3 from (A)]. Tys 14^CCR5 is shown in purple, with Tys 100c^412d in red. Select residues of gp120 are shown in stick representation and labeled in black. Hydrogen bonds coordinating the buried sulfate groups in each are depicted with dotted lines.
 
  The above figures are reprinted by permission from the AAAs: Science (2007, 317, 1930-1934) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference
  PubMed id Reference
19478876 B.Dey, K.Svehla, L.Xu, D.Wycuff, T.Zhou, G.Voss, A.Phogat, B.K.Chakrabarti, Y.Li, G.Shaw, P.D.Kwong, G.J.Nabel, J.R.Mascola, and R.T.Wyatt (2009).
Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site.
  PLoS Pathog, 5, e1000445.  
19390419 B.L.Walter, A.E.Armitage, S.C.Graham, T.de Oliveira, P.Skinhøj, E.Y.Jones, D.I.Stuart, A.J.McMichael, B.Chesebro, and A.K.Iversen (2009).
Functional characteristics of HIV-1 subtype C compatible with increased heterosexual transmissibility.
  AIDS, 23, 1047-1057.  
19339951 D.E.Mosier (2009).
How HIV changes its tropism: evolution and adaptation?
  Curr Opin HIV AIDS, 4, 125-130.  
19339946 D.T.Lodowski, and K.Palczewski (2009).
Chemokine receptors and other G protein-coupled receptors.
  Curr Opin HIV AIDS, 4, 88-95.  
19734912 F.Baleux, L.Loureiro-Morais, Y.Hersant, P.Clayette, F.Arenzana-Seisdedos, D.Bonnaffé, and H.Lortat-Jacob (2009).
A synthetic CD4-heparan sulfate glycoconjugate inhibits CCR5 and CXCR4 HIV-1 attachment and entry.
  Nat Chem Biol, 5, 743-748.  
19339950 J.P.Moore, and D.R.Kuritzkes (2009).
A pièce de resistance: how HIV-1 escapes small molecule CCR5 inhibitors.
  Curr Opin HIV AIDS, 4, 118-124.  
19279325 J.da Silva (2009).
Amino Acid covariation in a functionally important human immunodeficiency virus type 1 protein region is associated with population subdivision.
  Genetics, 182, 265-275.  
19019969 K.L.Davis, F.Bibollet-Ruche, H.Li, J.M.Decker, O.Kutsch, L.Morris, A.Salomon, A.Pinter, J.A.Hoxie, B.H.Hahn, P.D.Kwong, and G.M.Shaw (2009).
Human immunodeficiency virus type 2 (HIV-2)/HIV-1 envelope chimeras detect high titers of broadly reactive HIV-1 V3-specific antibodies in human plasma.
  J Virol, 83, 1240-1259.  
19193800 K.M.Nolan, G.Q.Del Prete, A.P.Jordan, B.Haggarty, J.Romano, G.J.Leslie, and J.A.Hoxie (2009).
Characterization of a human immunodeficiency virus type 1 V3 deletion mutation that confers resistance to CCR5 inhibitors and the ability to use aplaviroc-bound receptor.
  J Virol, 83, 3798-3809.  
  19920903 N.Ray (2009).
Maraviroc in the treatment of HIV infection.
  Drug Des Devel Ther, 2, 151-161.  
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.  
19448659 P.D.Kwong, and I.A.Wilson (2009).
HIV-1 and influenza antibodies: seeing antigens in new ways.
  Nat Immunol, 10, 573-578.  
19680536 R.Berro, R.W.Sanders, M.Lu, P.J.Klasse, and J.P.Moore (2009).
Two HIV-1 variants resistant to small molecule CCR5 inhibitors differ in how they use CCR5 for entry.
  PLoS Pathog, 5, e1000548.  
18815291 T.Ghosh, K.Chattopadhyay, M.Marschall, P.Karmakar, P.Mandal, and B.Ray (2009).
Focus on antivirally active sulfated polysaccharides: from structure-activity analysis to clinical evaluation.
  Glycobiology, 19, 2.  
19339948 W.C.Olson, and J.M.Jacobson (2009).
CCR5 monoclonal antibodies for HIV-1 therapy.
  Curr Opin HIV AIDS, 4, 104-111.  
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
18765264 B.M.Chain, M.Noursadeghi, M.Gardener, J.Tsang, and E.Wright (2008).
HIV blocking antibodies following immunisation with chimaeric peptides coding a short N-terminal sequence of the CCR5 receptor.
  Vaccine, 26, 5752-5759.  
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.  
18256149 C.Pastori, A.Clivio, L.Diomede, R.Consonni, G.M.De Mori, R.Longhi, G.Colombo, and L.Lopalco (2008).
Two amino acid substitutions within the first external loop of CCR5 induce human immunodeficiency virus-blocking antibodies in mice and chickens.
  J Virol, 82, 4125-4134.  
18516039 E.J.Adams, P.Strop, S.Shin, Y.H.Chien, and K.C.Garcia (2008).
An autonomous CDR3delta is sufficient for recognition of the nonclassical MHC class I molecules T10 and T22 by gammadelta T cells.
  Nat Immunol, 9, 777-784.  
18799588 J.E.Harrison, J.B.Lynch, L.J.Sierra, L.A.Blackburn, N.Ray, R.G.Collman, and R.W.Doms (2008).
Baseline resistance of primary human immunodeficiency virus type 1 strains to the CXCR4 inhibitor AMD3100.
  J Virol, 82, 11695-11704.  
18507530 K.Michler, B.J.Connell, W.D.Venter, W.S.Stevens, A.Capovilla, and M.A.Papathanasopoulos (2008).
Genotypic characterization and comparison of full-length envelope glycoproteins from South African HIV type 1 subtype C primary isolates that utilize CCR5 and/or CXCR4.
  AIDS Res Hum Retroviruses, 24, 743-751.  
18833294 M.N.Forsell, B.Dey, A.Mörner, K.Svehla, S.O'dell, C.M.Högerkorp, G.Voss, R.Thorstensson, G.M.Shaw, J.R.Mascola, G.B.Karlsson Hedestam, and R.T.Wyatt (2008).
B cell recognition of the conserved HIV-1 co-receptor binding site is altered by endogenous primate CD4.
  PLoS Pathog, 4, e1000171.  
18787705 S.Naganawa, M.Yokoyama, T.Shiino, T.Suzuki, Y.Ishigatsubo, A.Ueda, A.Shirai, M.Takeno, S.Hayakawa, S.Sato, O.Tochikubo, S.Kiyoura, K.Sawada, T.Ikegami, T.Kanda, K.Kitamura, and H.Sato (2008).
Net positive charge of HIV-1 CRF01_AE V3 sequence regulates viral sensitivity to humoral immunity.
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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.