PDBsum entry 1zec

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Viral peptide PDB id
Protein chain
27 a.a.
PDB id:
Name: Viral peptide
Title: Nmr solution structure of nef1-25, 20 structures
Structure: Nef1-25. Chain: a. Fragment: n-terminal fragment of nef. Engineered: yes
Source: Human immunodeficiency virus 1. Organism_taxid: 11676. Gene: n-terminal fragment of. Expressed in: escherichia coli. Expression_system_taxid: 562
NMR struc: 20 models
Authors: K.J.Barnham,S.A.Monks,M.G.Hinds,A.A.Azad,R.S.Norton
Key ref:
K.J.Barnham et al. (1997). Solution structure of a polypeptide from the N terminus of the HIV protein Nef. Biochemistry, 36, 5970-5980. PubMed id: 9166767 DOI: 10.1021/bi9629945
18-Dec-96     Release date:   07-Jan-98    
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Protein chain
Pfam   ArchSchema ?
P03404  (NEF_HV1B1) -  Protein Nef
206 a.a.
26 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)


DOI no: 10.1021/bi9629945 Biochemistry 36:5970-5980 (1997)
PubMed id: 9166767  
Solution structure of a polypeptide from the N terminus of the HIV protein Nef.
K.J.Barnham, S.A.Monks, M.G.Hinds, A.A.Azad, R.S.Norton.
Nef is a 27 kDa myristylated phosphoprotein expressed early in infection by HIV. The N terminus of Nef is thought to play a vital role in the functions of this protein through its interactions with membrane structures. The solution structure of a 25-residue polypeptide corresponding to the N terminus of Nef (Nef1-25) has been investigated by 1H NMR spectroscopy. In aqueous solution at pH 4.8 and 281 K, this peptide underwent conformational averaging, with Pro13 existing in cis and trans conformations in nearly equal proportions. In methanol solution, however, the peptide adopted a well-defined alpha-helical structure from residues 6 to 22, with the N- and C-terminal regions having a less ordered structure. On the basis of a comparison of chemical shifts and NOEs, it appeared that this helical structure was maintained in aqueous trifluoroethanol (50% v/v) and to a lesser extent in a solution of SDS micelles. When the N-acetyl group was replaced by either an N-myristyl or a free ammonium group, there was little effect on the three-dimensional structure of the peptide in methanol; deamidation of the C terminus also had no effect on the structure in methanol. In water, the myristylated peptide aggregated. The similarity between the sequences of Nef1-25 and melittin is reflected in the similar structures of the two molecules, although the N-terminal helix of melittin is more defined. This similarity in structure raises the possibility that Nef1-25 not only interacts with membranes but also may be capable of disrupting them and causing cell lysis. This type of interaction could contribute at least in part to the killing of bystander cells in lymphoid tissues during HIV infection.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21365684 J.Jung, I.J.Byeon, J.Ahn, and A.M.Gronenborn (2011).
Structure, dynamics, and Hck interaction of full-length HIV-1 Nef.
  Proteins, 79, 1609-1622.  
19935658 H.Gerlach, V.Laumann, S.Martens, C.F.Becker, R.S.Goody, and M.Geyer (2010).
HIV-1 Nef membrane association depends on charge, curvature, composition and sequence.
  Nat Chem Biol, 6, 46-53.  
19383468 R.Szilluweit, A.Boll, S.Lukowski, H.Gerlach, O.T.Fackler, M.Geyer, and C.Steinem (2009).
HIV-1 Nef perturbs artificial membranes: investigation of the contribution of the myristoyl anchor.
  Biophys J, 96, 3242-3250.  
18191978 M.Qi, and C.Aiken (2008).
Nef enhances HIV-1 infectivity via association with the virus assembly complex.
  Virology, 373, 287-297.  
17182689 G.Mangino, Z.A.Percario, G.Fiorucci, G.Vaccari, S.Manrique, G.Romeo, M.Federico, M.Geyer, and E.Affabris (2007).
In vitro treatment of human monocytes/macrophages with myristoylated recombinant Nef of human immunodeficiency virus type 1 leads to the activation of mitogen-activated protein kinases, IkappaB kinases, and interferon regulatory factor 3 and to the release of beta interferon.
  J Virol, 81, 2777-2791.  
17114219 H.Raghuraman, and A.Chattopadhyay (2007).
Orientation and dynamics of melittin in membranes of varying composition utilizing NBD fluorescence.
  Biophys J, 92, 1271-1283.  
17139559 H.Raghuraman, and A.Chattopadhyay (2007).
Melittin: a membrane-active peptide with diverse functions.
  Biosci Rep, 27, 189-223.  
16021629 C.A.Dennis, A.Baron, J.G.Grossmann, S.Mazaleyrat, M.Harris, and J.Jaeger (2005).
Co-translational myristoylation alters the quaternary structure of HIV-1 Nef in solution.
  Proteins, 60, 658-669.  
15632291 M.Matsubara, T.Jing, K.Kawamura, N.Shimojo, K.Titani, K.Hashimoto, and N.Hayashi (2005).
Myristoyl moiety of HIV Nef is involved in regulation of the interaction with calmodulin in vivo.
  Protein Sci, 14, 494-503.  
15546886 X.Lauth, J.J.Babon, J.A.Stannard, S.Singh, V.Nizet, J.M.Carlberg, V.E.Ostland, M.W.Pennington, R.S.Norton, and M.E.Westerman (2005).
Bass hepcidin synthesis, solution structure, antimicrobial activities and synergism, and in vivo hepatic response to bacterial infections.
  J Biol Chem, 280, 9272-9282.
PDB code: 1s6w
15454440 H.Raghuraman, and A.Chattopadhyay (2004).
Interaction of melittin with membrane cholesterol: a fluorescence approach.
  Biophys J, 87, 2419-2432.  
15071759 H.Raghuraman, and A.Chattopadhyay (2004).
Effect of micellar charge on the conformation and dynamics of melittin.
  Eur Biophys J, 33, 611-622.  
12163596 K.Yusim, C.Kesmir, B.Gaschen, M.M.Addo, M.Altfeld, S.Brunak, A.Chigaev, V.Detours, and B.T.Korber (2002).
Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1 (HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variation.
  J Virol, 76, 8757-8768.  
10684310 H.Akari, S.Arold, T.Fukumori, T.Okazaki, K.Strebel, and A.Adachi (2000).
Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation.
  J Virol, 74, 2907-2912.  
  10892807 S.Arold, F.Hoh, S.Domergue, C.Birck, M.A.Delsuc, M.Jullien, and C.Dumas (2000).
Characterization and molecular basis of the oligomeric structure of HIV-1 nef protein.
  Protein Sci, 9, 1137-1148.  
  9971776 A.Mangasarian, V.Piguet, J.K.Wang, Y.L.Chen, and D.Trono (1999).
Nef-induced CD4 and major histocompatibility complex class I (MHC-I) down-regulation are governed by distinct determinants: N-terminal alpha helix and proline repeat of Nef selectively regulate MHC-I trafficking.
  J Virol, 73, 1964-1973.  
10386338 V.Piguet, and D.Trono (1999).
The Nef protein of primate lentiviruses.
  Rev Med Virol, 9, 111-120.  
  9840287 C.C.Curtain, M.G.Lowe, I.G.Macreadie, I.R.Gentle, G.A.Lawrie, and A.A.Azad (1998).
Structural requirements for the cytotoxicity of the N-terminal region of HIV type 1 Nef.
  AIDS Res Hum Retroviruses, 14, 1543-1551.  
9678491 I.G.Macreadie, R.Fernley, L.A.Castelli, A.Lucantoni, J.White, and A.Azad (1998).
Expression of HIV-1 nef in yeast causes membrane perturbation and release of the myristylated Nef protein.
  J Biomed Sci, 5, 203-210.  
9545423 K.Natarajan, and J.A.Cowan (1998).
Solution structure of a synthetic lytic peptide: the perforin amino terminus.
  Chem Biol, 5, 147-154.  
9851370 S.Yao, A.M.Torres, A.A.Azad, I.G.Macreadie, and R.S.Norton (1998).
Solution structure of peptides from HIV-1 Vpr protein that cause membrane permeabilization and growth arrest.
  J Pept Sci, 4, 426-435.
PDB codes: 1bde 1dsk
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