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PDBsum entry 1qa5
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Viral protein
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PDB id
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1qa5
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Contents |
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* Residue conservation analysis
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DOI no:
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J Mol Biol
289:123-138
(1999)
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PubMed id:
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Structure of the anchor-domain of myristoylated and non-myristoylated HIV-1 Nef protein.
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M.Geyer,
C.E.Munte,
J.Schorr,
R.Kellner,
H.R.Kalbitzer.
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ABSTRACT
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Negative factor (Nef) is a regulatory myristoylated protein of human
immunodeficiency virus (HIV) that has a two-domain structure consisting of an
anchor domain and a core domain separated by a specific cleavage site of the HIV
proteases. For structural analysis, the HIV-1 Nef anchor domain (residues 2-57)
was synthesized with a myristoylated and non-myristoylated N terminus. The
structures of the two peptides were studied by1H NMR spectroscopy and a
structural model was obtained by restrained molecular dynamic simulations. The
non-myristoylated peptide does not have a unique, compactly folded structure but
occurs in a relatively extended conformation. The only rather well-defined
canonical secondary structure element is a short two-turn alpha-helix (H2)
between Arg35 and Gly41. A tendency for another helical secondary structure
element (H1) can be observed for the arginine-rich region (Arg17 to Arg22).
Myristoylation of the N-terminal glycine residue leads to stabilization of both
helices, H1 and H2. The first helix in the arginine-rich region is stabilized by
the myristoylation and now contains residues Pro14 to Arg22. The second helix
appears to be better defined and to contain more residues (Ala33 to Gly41) than
in the absence of myristoylation. In addition, the hydrophobic N-terminal
myristic acid residue interacts closely with the side-chain of Trp5 and thereby
forms a loop with Gly2, Gly3 and Lys4 in the kink region. This interaction could
possibly be disturbed by phosphorylation of a nearby serine residue, and modifiy
the characteristic membrane interactions of the HIV-1 Nef anchor domain.
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Selected figure(s)
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
289,
123-138)
copyright 1999.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.Jung,
I.J.Byeon,
J.Ahn,
and
A.M.Gronenborn
(2011).
Structure, dynamics, and Hck interaction of full-length HIV-1 Nef.
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Proteins,
79,
1609-1622.
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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.
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Nat Chem Biol,
6,
46-53.
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S.A.Ali,
M.B.Huang,
P.E.Campbell,
W.W.Roth,
T.Campbell,
M.Khan,
G.Newman,
F.Villinger,
M.D.Powell,
and
V.C.Bond
(2010).
Genetic characterization of HIV type 1 Nef-induced vesicle secretion.
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AIDS Res Hum Retroviruses,
26,
173-192.
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Y.J.Jin,
X.Zhang,
C.Y.Cai,
and
S.J.Burakoff
(2010).
Alkylating HIV-1 Nef - a potential way of HIV intervention.
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AIDS Res Ther,
7,
26.
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Y.T.Kwak,
A.Raney,
L.S.Kuo,
S.J.Denial,
B.R.Temple,
J.V.Garcia,
and
J.L.Foster
(2010).
Self-association of the Lentivirus protein, Nef.
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Retrovirology,
7,
77.
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C.Marusic,
A.Vitale,
E.Pedrazzini,
M.Donini,
L.Frigerio,
R.Bock,
P.J.Dix,
M.S.McCabe,
M.Bellucci,
and
E.Benvenuto
(2009).
Plant-based strategies aimed at expressing HIV antigens and neutralizing antibodies at high levels. Nef as a case study.
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Transgenic Res,
18,
499-512.
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R.K.Singh,
D.Lau,
C.M.Noviello,
P.Ghosh,
and
J.C.Guatelli
(2009).
An MHC-I cytoplasmic domain/HIV-1 Nef fusion protein binds directly to the micro subunit of the AP-1 endosomal coat complex.
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PLoS One,
4,
e8364.
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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.
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Biophys J,
96,
3242-3250.
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W.Ma,
S.Mishra,
N.Gajanayaka,
J.B.Angel,
and
A.Kumar
(2009).
HIV-1 Nef inhibits lipopolysaccharide-induced IL-12p40 expression by inhibiting JNK-activated NFkappaB in human monocytic cells.
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J Biol Chem,
284,
7578-7587.
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C.M.Noviello,
S.Benichou,
and
J.C.Guatelli
(2008).
Cooperative binding of the class I major histocompatibility complex cytoplasmic domain and human immunodeficiency virus type 1 Nef to the endosomal AP-1 complex via its mu subunit.
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J Virol,
82,
1249-1258.
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C.S.Park,
D.H.Lee,
K.M.Lee,
and
C.H.Lee
(2008).
Characterization and signature pattern analysis of Korean clade HIV-1 using nef gene sequences.
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J Microbiol,
46,
88-94.
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O.W.Lindwasser,
W.J.Smith,
R.Chaudhuri,
P.Yang,
J.H.Hurley,
and
J.S.Bonifacino
(2008).
A diacidic motif in human immunodeficiency virus type 1 Nef is a novel determinant of binding to AP-2.
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J Virol,
82,
1166-1174.
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A.Raney,
A.Y.Shaw,
J.L.Foster,
and
J.V.Garcia
(2007).
Structural constraints on human immunodeficiency virus type 1 Nef function.
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Virology,
368,
7.
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C.Marusic,
J.Nuttall,
G.Buriani,
C.Lico,
R.Lombardi,
S.Baschieri,
E.Benvenuto,
and
L.Frigerio
(2007).
Expression, intracellular targeting and purification of HIV Nef variants in tobacco cells.
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BMC Biotechnol,
7,
12.
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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.
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J Virol,
81,
2777-2791.
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P.R.Walker,
M.Ketunuti,
I.A.Choge,
T.Meyers,
G.Gray,
E.C.Holmes,
and
L.Morris
(2007).
Polymorphisms in Nef associated with different clinical outcomes in HIV type 1 subtype C-infected children.
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AIDS Res Hum Retroviruses,
23,
204-215.
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A.Crotti,
F.Neri,
D.Corti,
S.Ghezzi,
S.Heltai,
A.Baur,
G.Poli,
E.Santagostino,
and
E.Vicenzi
(2006).
Nef alleles from human immunodeficiency virus type 1-infected long-term-nonprogressor hemophiliacs with or without late disease progression are defective in enhancing virus replication and CD4 down-regulation.
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J Virol,
80,
10663-10674.
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A.Schönichen,
M.Alexander,
J.E.Gasteier,
F.E.Cuesta,
O.T.Fackler,
and
M.Geyer
(2006).
Biochemical characterization of the diaphanous autoregulatory interaction in the formin homology protein FHOD1.
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J Biol Chem,
281,
5084-5093.
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J.F.Roeth,
and
K.L.Collins
(2006).
Human immunodeficiency virus type 1 Nef: adapting to intracellular trafficking pathways.
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Microbiol Mol Biol Rev,
70,
548-563.
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M.Kumar,
S.K.Jain,
S.T.Pasha,
D.Chattopadhaya,
S.Lal,
and
A.Rai
(2006).
Genomic diversity in the regulatory nef gene sequences in Indian isolates of HIV type 1: emergence of a distinct subclade and predicted implications.
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AIDS Res Hum Retroviruses,
22,
1206-1219.
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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.
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Proteins,
60,
658-669.
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A.Olszewski,
K.Sato,
Z.D.Aron,
F.Cohen,
A.Harris,
B.R.McDougall,
W.E.Robinson,
L.E.Overman,
and
G.A.Weiss
(2004).
Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck.
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Proc Natl Acad Sci U S A,
101,
14079-14084.
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O.Peleg,
E.N.Trifonov,
and
A.Bolshoy
(2003).
Hidden messages in the nef gene of human immunodeficiency virus type 1 suggest a novel RNA secondary structure.
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Nucleic Acids Res,
31,
4192-4200.
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V.N.Uversky
(2002).
Natively unfolded proteins: a point where biology waits for physics.
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Protein Sci,
11,
739-756.
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M.Geyer,
O.T.Fackler,
and
B.M.Peterlin
(2001).
Structure--function relationships in HIV-1 Nef.
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EMBO Rep,
2,
580-585.
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O.T.Fackler,
D.Wolf,
H.O.Weber,
B.Laffert,
P.D'Aloja,
B.Schuler-Thurner,
R.Geffin,
K.Saksela,
M.Geyer,
B.M.Peterlin,
G.Schuler,
and
A.S.Baur
(2001).
A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells.
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Curr Biol,
11,
1294-1299.
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R.Mandic,
O.T.Fackler,
M.Geyer,
T.Linnemann,
Y.H.Zheng,
and
B.M.Peterlin
(2001).
Negative factor from SIV binds to the catalytic subunit of the V-ATPase to internalize CD4 and to increase viral infectivity.
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Mol Biol Cell,
12,
463-473.
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S.H.Coleman,
J.R.Day,
and
J.C.Guatelli
(2001).
The HIV-1 Nef protein as a target for antiretroviral therapy.
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Expert Opin Ther Targets,
5,
1.
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S.T.Arold,
and
A.S.Baur
(2001).
Dynamic Nef and Nef dynamics: how structure could explain the complex activities of this small HIV protein.
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Trends Biochem Sci,
26,
356-363.
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D.E.Wakeham,
J.A.Ybe,
F.M.Brodsky,
and
P.K.Hwang
(2000).
Molecular structures of proteins involved in vesicle coat formation.
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Traffic,
1,
393-398.
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J.A.Losonczi,
F.Tian,
and
J.H.Prestegard
(2000).
Nuclear magnetic resonance studies of the N-terminal fragment of adenosine diphosphate ribosylation factor 1 in micelles and bicelles: influence of N-myristoylation.
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Biochemistry,
39,
3804-3816.
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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.
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Protein Sci,
9,
1137-1148.
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V.N.Uversky,
J.R.Gillespie,
and
A.L.Fink
(2000).
Why are "natively unfolded" proteins unstructured under physiologic conditions?
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Proteins,
41,
415-427.
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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.
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Links
