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PDBsum entry 1lcx
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Viral protein PDB id
1lcx

 

 

 

 

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Contents
Protein chain
13 a.a.
PDB id:
1lcx
Name: Viral protein
Title: Nmr structure of HIV-1 gp41 659-671 13mer peptide
Structure: Gp41. Chain: a. Fragment: residues 659-671. Synonym: transmembrane glycoprotein. Engineered: yes
Source: Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence of the peptide is naturally found in HIV-1 virus.
NMR struc: 25 models
Authors: Z.Biron,S.Khare,A.O.Samson,Y.Hayek,F.Naider,J.Anglister
Key ref:
Z.Biron et al. (2002). A monomeric 3(10)-helix is formed in water by a 13-residue peptide representing the neutralizing determinant of HIV-1 on gp41. Biochemistry, 41, 12687-12696. PubMed id: 12379111 DOI: 10.1021/bi026261y
Date:
07-Apr-02     Release date:   04-Dec-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P31872  (ENV_HV1W1) -  Envelope glycoprotein gp160 from Human immunodeficiency virus type 1 group M subtype B (isolate WMJ1)
Seq:
Struc: 		 
Seq:
Struc: 		856 a.a.
13 a.a.
Key:    PfamA domain  Secondary structure

 

 
DOI no: 10.1021/bi026261y Biochemistry 41:12687-12696 (2002)
PubMed id: 12379111  
 
 
A monomeric 3(10)-helix is formed in water by a 13-residue peptide representing the neutralizing determinant of HIV-1 on gp41.
Z.Biron, S.Khare, A.O.Samson, Y.Hayek, F.Naider, J.Anglister.
 
  ABSTRACT  
 
The peptide gp41(659-671) (ELLELDKWASLWN) comprises the entire epitope for one of the three known antibodies capable of neutralizing a broad spectrum of primary HIV-1 isolates and is the only such epitope that is sequential. Here we present the NMR structure of gp41(659-671) in water. This peptide forms a monomeric 3(10)-helix stabilized by i,i+3 side chain-side chain interactions favored by its primary sequence. In this conformation the peptide presents an exposed surface, which is mostly hydrophobic and consists of conserved HIV-1 residues. The presence of the 3(10)-helix is confirmed by its characteristic CD pattern. Studies of the 3(10)-helix have been hampered by the absence of a model peptide adopting this conformation. gp41(659-671) can serve as such a model to investigate the spectral characteristics of the 3(10)-helix, the factors that influence its stability, and the propensity of different amino acids to form a 3(10)-helix. The observation that the 3(10)-helical conformation is highly populated in the peptide gp41(659-671) indicates that the corresponding segment in the cognate protein is an autonomous folding unit. As such, it is very likely that the helical conformation is maintained in gp41 throughout the different tertiary structures of the envelope protein that form during the process of viral fusion. However, the exposure of the gp41(659-671) segment may vary, leading to changes in the reactivity of anti-gp41 antibodies in the different stages of viral fusion. Since gp41(659-671) is an autonomous folding unit, peptide immunogens consisting of the complete gp41(659-671) sequence are likely to induce antibodies highly cross-reactive with HIV-1.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21057682 C.R.Gregor, E.Cerasoli, P.R.Tulip, M.G.Ryadnov, G.J.Martyna, and J.Crain (2011).
Autonomous folding in the membrane proximal HIV peptide gp41(659-671): pH tuneability at micelle interfaces.
  Phys Chem Chem Phys, 13, 127-135.  
21207612 Y.Singh, P.C.Sharpe, H.N.Hoang, A.J.Lucke, A.W.McDowall, S.P.Bottomley, and D.P.Fairlie (2011).
Amyloid formation from an α-helix peptide bundle is seeded by 3(10)-helix aggregates.
  Chemistry, 17, 151-160.  
21038394 F.Formaggio, and C.Toniolo (2010).
Electronic and vibrational signatures of peptide helical structures: A tribute to Anton Mario Tamburro.
  Chirality, 22, E30-E39.  
20876137 G.Ofek, F.J.Guenaga, W.R.Schief, J.Skinner, D.Baker, R.Wyatt, and P.D.Kwong (2010).
Elicitation of structure-specific antibodies by epitope scaffolds.
  Proc Natl Acad Sci U S A, 107, 17880-17887.
PDB codes: 3les 3lev 3lex 3ley
20042512 G.Ofek, K.McKee, Y.Yang, Z.Y.Yang, J.Skinner, F.J.Guenaga, R.Wyatt, M.B.Zwick, G.J.Nabel, J.R.Mascola, and P.D.Kwong (2010).
Relationship between antibody 2F5 neutralization of HIV-1 and hydrophobicity of its heavy chain third complementarity-determining region.
  J Virol, 84, 2955-2962.  
20138057 M.Lapelosa, G.F.Arnold, E.Gallicchio, E.Arnold, and R.M.Levy (2010).
Antigenic characteristics of rhinovirus chimeras designed in silico for enhanced presentation of HIV-1 gp41 epitopes [corrected].
  J Mol Biol, 397, 752-766.  
19279101 G.F.Arnold, P.K.Velasco, A.K.Holmes, T.Wrin, S.C.Geisler, P.Phung, Y.Tian, D.A.Resnick, X.Ma, T.M.Mariano, C.J.Petropoulos, J.W.Taylor, H.Katinger, and E.Arnold (2009).
Broad neutralization of human immunodeficiency virus type 1 (HIV-1) elicited from human rhinoviruses that display the HIV-1 gp41 ELDKWA epitope.
  J Virol, 83, 5087-5100.  
19026659 M.Lapelosa, E.Gallicchio, G.F.Arnold, E.Arnold, and R.M.Levy (2009).
In silico vaccine design based on molecular simulations of rhinovirus chimeras presenting HIV-1 gp41 epitopes.
  J Mol Biol, 385, 675-691.  
19297617 P.Ingallinella, E.Bianchi, N.A.Ladwa, Y.J.Wang, R.Hrin, M.Veneziano, F.Bonelli, T.J.Ketas, J.P.Moore, M.D.Miller, and A.Pessi (2009).
Addition of a cholesterol group to an HIV-1 peptide fusion inhibitor dramatically increases its antiviral potency.
  Proc Natl Acad Sci U S A, 106, 5801-5806.  
19515770 R.Pejchal, J.S.Gach, F.M.Brunel, R.M.Cardoso, R.L.Stanfield, P.E.Dawson, D.R.Burton, M.B.Zwick, and I.A.Wilson (2009).
A conformational switch in human immunodeficiency virus gp41 revealed by the structures of overlapping epitopes recognized by neutralizing antibodies.
  J Virol, 83, 8451-8462.
PDB code: 3fn0
19740978 S.Bryson, J.P.Julien, R.C.Hynes, and E.F.Pai (2009).
Crystallographic definition of the epitope promiscuity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5: vaccine design implications.
  J Virol, 83, 11862-11875.
PDB codes: 1u8h 1u8i 1u8j 1u8l 1u8m 1u8n 1u8o 1u8p 1u8q 1u91 1u92 1u93 1u95 2f5a 2f5b 2pw1 2pw2 3idg 3idi 3idj 3idm 3idn
19906992 S.M.Alam, M.Morelli, S.M.Dennison, H.X.Liao, R.Zhang, S.M.Xia, S.Rits-Volloch, L.Sun, S.C.Harrison, B.F.Haynes, and B.Chen (2009).
Role of HIV membrane in neutralization by two broadly neutralizing antibodies.
  Proc Natl Acad Sci U S A, 106, 20234-20239.  
18932268 Z.Ahmed, J.P.Scaffidi, and S.A.Asher (2009).
Circular dichroism and UV-resonance Raman investigation of the temperature dependence of the conformations of linear and cyclic elastin.
  Biopolymers, 91, 52-60.  
18068750 A.Penn-Nicholson, D.P.Han, S.J.Kim, H.Park, R.Ansari, D.C.Montefiori, and M.W.Cho (2008).
Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope.
  Virology, 372, 442-456.  
18540633 E.Noah, Z.Biron, F.Naider, B.Arshava, and J.Anglister (2008).
The membrane proximal external region of the HIV-1 envelope glycoprotein gp41 contributes to the stabilization of the six-helix bundle formed with a matching N' peptide.
  Biochemistry, 47, 6782-6792.  
18596094 N.Huarte, M.Lorizate, R.Maeso, R.Kunert, R.Arranz, J.M.Valpuesta, and J.L.Nieva (2008).
The broadly neutralizing anti-human immunodeficiency virus type 1 4E10 monoclonal antibody is better adapted to membrane-bound epitope recognition and blocking than 2F5.
  J Virol, 82, 8986-8996.  
18353966 S.A.Vishwanathan, and E.Hunter (2008).
Importance of the membrane-perturbing properties of the membrane-proximal external region of human immunodeficiency virus type 1 gp41 to viral fusion.
  J Virol, 82, 5118-5126.  
17055621 M.Kim, Z.Qiao, J.Yu, D.Montefiori, and E.L.Reinherz (2007).
Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state.
  Vaccine, 25, 5102-5114.  
17267498 M.Law, R.M.Cardoso, I.A.Wilson, and D.R.Burton (2007).
Antigenic and immunogenic study of membrane-proximal external region-grafted gp120 antigens by a DNA prime-protein boost immunization strategy.
  J Virol, 81, 4272-4285.  
17331029 P.W.Mobley, J.A.Barry, A.J.Waring, M.A.Sherman, and L.M.Gordon (2007).
Membrane perturbing actions of HIV type 1 glycoprotein 41 domains are inhibited by helical C-peptides.
  AIDS Res Hum Retroviruses, 23, 224-242.  
16501112 E.Yuste, H.B.Sanford, J.Carmody, J.Bixby, S.Little, M.B.Zwick, T.Greenough, D.R.Burton, D.D.Richman, R.C.Desrosiers, and W.E.Johnson (2006).
Simian immunodeficiency virus engrafted with human immunodeficiency virus type 1 (HIV-1)-specific epitopes: replication, neutralization, and survey of HIV-1-positive plasma.
  J Virol, 80, 3030-3041.  
16687410 K.Oresic, V.Noriega, L.Andrews, and D.Tortorella (2006).
A structural determinant of human cytomegalovirus US2 dictates the down-regulation of class I major histocompatibility molecules.
  J Biol Chem, 281, 19395-19406.  
16302220 M.Arai, and M.Iwakura (2006).
Peptide fragment studies on the folding elements of dihydrofolate reductase from Escherichia coli.
  Proteins, 62, 399-410.  
16700558 S.Hirosue, and T.Weber (2006).
pH-Dependent lytic peptides discovered by phage display.
  Biochemistry, 45, 6476-6487.  
16455666 Y.Wexler-Cohen, B.T.Johnson, A.Puri, R.Blumenthal, and Y.Shai (2006).
Structurally altered peptides reveal an important role for N-terminal heptad repeat binding and stability in the inhibitory action of HIV-1 peptide DP178.
  J Biol Chem, 281, 9005-9010.  
15708846 E.E.Büllesbach, and C.Schwabe (2005).
LGR8 signal activation by the relaxin-like factor.
  J Biol Chem, 280, 14586-14590.  
15633206 E.Schievano, K.Pagano, S.Mammi, and E.Peggion (2005).
Conformational studies of Aib-rich peptides containing lactam-bridged side chains: evidence of 3(10)-helix formation.
  Biopolymers, 80, 294-302.  
15613352 M.B.Zwick, R.Jensen, S.Church, M.Wang, G.Stiegler, R.Kunert, H.Katinger, and D.R.Burton (2005).
Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1.
  J Virol, 79, 1252-1261.  
16227780 M.B.Zwick (2005).
The membrane-proximal external region of HIV-1 gp41: a vaccine target worth exploring.
  AIDS, 19, 1725-1737.  
14963170 E.de Rosny, R.Vassell, S.Jiang, R.Kunert, and C.D.Weiss (2004).
Binding of the 2F5 monoclonal antibody to native and fusion-intermediate forms of human immunodeficiency virus type 1 gp41: implications for fusion-inducing conformational changes.
  J Virol, 78, 2627-2631.  
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
12646555 S.G.Peisajovich, S.A.Gallo, R.Blumenthal, and Y.Shai (2003).
C-terminal octylation rescues an inactive T20 mutant: implications for the mechanism of HIV/SIMIAN immunodeficiency virus-induced membrane fusion.
  J Biol Chem, 278, 21012-21017.  
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.

 

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