|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Proc Natl Acad Sci U S A
95:6941-6946
(1998)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Crystal structure of chemically synthesized [N33A] stromal cell-derived factor 1alpha, a potent ligand for the HIV-1 "fusin" coreceptor.
|
|
C.Dealwis,
E.J.Fernandez,
D.A.Thompson,
R.J.Simon,
M.A.Siani,
E.Lolis.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Stromal cell-derived factor-1alpha (SDF-1alpha ) is a member of the chemokine
superfamily and functions as a growth factor and chemoattractant through
activation of CXCR4/LESTR/Fusin, a G protein-coupled receptor. This receptor
also functions as a coreceptor for T-tropic syncytium-inducing strains of HIV-1.
SDF-1alpha antagonizes infectivity of these strains by competing with gp120 for
binding to the receptor. The crystal structure of a variant SDF-1alpha
([N33A]SDF-1alpha ) prepared by total chemical synthesis has been refined to
2.2-A resolution. Although SDF-1alpha adopts a typical chemokine
beta-beta-beta-alpha topology, the packing of the alpha-helix against the
beta-sheet is strikingly different. Comparison of SDF-1alpha with other
chemokine structures confirms the hypothesis that SDF-1alpha may be either an
ancestral protein from which all other chemokines evolved or the chemokine that
is the least divergent from a primordial chemokine. The structure of SDF-1alpha
reveals a positively charged surface ideal for binding to the negatively charged
extracellular loops of the CXCR4 HIV-1 coreceptor. This ionic complementarity is
likely to promote the interaction of the mobile N-terminal segment of SDF-1alpha
with interhelical sites of the receptor, resulting in a biological response.
|
|
|
|
|
|
| |
Selected figure(s)
|
|
|
|
| |
|
|
|
|
|
|
Figure 1.
Fig. 1. (A) Structure of the SDF-1  dimer with
the secondary structure assignments for monomer 1 based on the
program INSIGHTII (Biosym Technologies, San Diego) shows the
extended N-terminal loop proceeding into the single turn of a
3[10] helix and strands  1, 2, and 3 followed
by the C-terminal helix packing almost orthogonally to the
three-stranded antiparallel -sheet. (B)
The IL-8 dimer is shown to highlight the differences between the
IL-8 and SDF-1 dimers.
|
|
Figure 2.
Fig. 2. 2F[o]-F[c] omit map contoured at 1  between
residues 25 to 41 that make up strands 1
and 2 and the interconnecting loop. The electron density for
monomer 1 (A25 to A41) is drawn in green and monomer 2 (B25 to
B41) is drawn in white. This figure was created with the
graphics program O (16).
|
|
|
|
| |
Figures were
selected
by an automated process.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
K.Bellmann-Sickert,
and
A.G.Beck-Sickinger
(2011).
Palmitoylated SDF1 α shows increased resistance against proteolytic degradation in liver homogenates.
|
| |
ChemMedChem,
6,
193-200.
|
|
|
|
|
|
|
B.Wu,
E.Y.Chien,
C.D.Mol,
G.Fenalti,
W.Liu,
V.Katritch,
R.Abagyan,
A.Brooun,
P.Wells,
F.C.Bi,
D.J.Hamel,
P.Kuhn,
T.M.Handel,
V.Cherezov,
and
R.C.Stevens
(2010).
Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists.
|
| |
Science,
330,
1066-1071.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
J.W.Murphy,
H.Yuan,
Y.Kong,
Y.Xiong,
and
E.J.Lolis
(2010).
Heterologous quaternary structure of CXCL12 and its relationship to the CC chemokine family.
|
| |
Proteins,
78,
1331-1337.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
K.Bellmann-Sickert,
L.Baumann,
and
A.G.Beck-Sickinger
(2010).
Selective labelling of stromal cell-derived factor 1α with carboxyfluorescein to study receptor internalisation.
|
| |
J Pept Sci,
16,
568-574.
|
|
|
|
|
|
|
A.Egorova,
A.Kiselev,
M.Hakli,
M.Ruponen,
V.Baranov,
and
A.Urtti
(2009).
Chemokine-derived peptides as carriers for gene delivery to CXCR4 expressing cells.
|
| |
J Gene Med,
11,
772-781.
|
|
|
|
|
|
|
C.T.Veldkamp,
J.J.Ziarek,
J.Su,
H.Basnet,
R.Lennertz,
J.J.Weiner,
F.C.Peterson,
J.E.Baker,
and
B.F.Volkman
(2009).
Monomeric structure of the cardioprotective chemokine SDF-1/CXCL12.
|
| |
Protein Sci,
18,
1359-1369.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
Y.Kofuku,
C.Yoshiura,
T.Ueda,
H.Terasawa,
T.Hirai,
S.Tominaga,
M.Hirose,
Y.Maeda,
H.Takahashi,
Y.Terashima,
K.Matsushima,
and
I.Shimada
(2009).
Structural basis of the interaction between chemokine stromal cell-derived factor-1/CXCL12 and its G-protein-coupled receptor CXCR4.
|
| |
J Biol Chem,
284,
35240-35250.
|
|
|
|
|
|
|
C.Zhonghua,
G.Chunpin,
Z.Yong,
X.Kezhi,
and
Z.Yaou
(2008).
Cloning and bioactivity analysis of a CXC ligand in black seabream Acanthopagrus schlegeli: the evolutionary clues of ELR+CXC chemokines.
|
| |
BMC Immunol,
9,
66.
|
|
|
|
|
|
|
S.Fermas,
F.Gonnet,
A.Sutton,
N.Charnaux,
B.Mulloy,
Y.Du,
F.Baleux,
and
R.Daniel
(2008).
Sulfated oligosaccharides (heparin and fucoidan) binding and dimerization of stromal cell-derived factor-1 (SDF-1/CXCL 12) are coupled as evidenced by affinity CE-MS analysis.
|
| |
Glycobiology,
18,
1054-1064.
|
|
|
|
|
|
|
X.Liang
(2008).
CXCR4, inhibitors and mechanisms of action.
|
| |
Chem Biol Drug Des,
72,
97.
|
|
|
|
|
|
|
C.Laguri,
R.Sadir,
P.Rueda,
F.Baleux,
P.Gans,
F.Arenzana-Seisdedos,
and
H.Lortat-Jacob
(2007).
The Novel CXCL12gamma Isoform Encodes an Unstructured Cationic Domain Which Regulates Bioactivity and Interaction with Both Glycosaminoglycans and CXCR4.
|
| |
PLoS ONE,
2,
e1110.
|
|
|
|
|
|
|
C.T.Veldkamp,
F.C.Peterson,
P.L.Hayes,
J.E.Mattmiller,
J.C.Haugner,
N.de la Cruz,
and
B.F.Volkman
(2007).
On-column refolding of recombinant chemokines for NMR studies and biological assays.
|
| |
Protein Expr Purif,
52,
202-209.
|
|
|
|
|
|
|
D.Liu,
N.Madani,
Y.Li,
R.Cao,
W.T.Choi,
S.P.Kawatkar,
M.Y.Lim,
S.Kumar,
C.Z.Dong,
J.Wang,
J.D.Russell,
C.R.Lefebure,
J.An,
S.Wilson,
Y.G.Gao,
L.A.Pallansch,
J.G.Sodroski,
and
Z.Huang
(2007).
Crystal structure and structural mechanism of a novel anti-human immunodeficiency virus and D-amino acid-containing chemokine.
|
| |
J Virol,
81,
11489-11498.
|
|
|
|
|
|
|
E.K.Ryu,
T.G.Kim,
T.H.Kwon,
I.D.Jung,
D.Ryu,
Y.M.Park,
J.Kim,
K.H.Ahn,
and
C.Ban
(2007).
Crystal structure of recombinant human stromal cell-derived factor-1alpha.
|
| |
Proteins,
67,
1193-1197.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.M.Busillo,
and
J.L.Benovic
(2007).
Regulation of CXCR4 signaling.
|
| |
Biochim Biophys Acta,
1768,
952-963.
|
|
|
|
|
|
|
C.T.Veldkamp,
C.Seibert,
F.C.Peterson,
T.P.Sakmar,
and
B.F.Volkman
(2006).
Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12).
|
| |
J Mol Biol,
359,
1400-1409.
|
|
|
|
|
|
|
K.Rajarathnam,
G.N.Prado,
H.Fernando,
I.Clark-Lewis,
and
J.Navarro
(2006).
Probing receptor binding activity of interleukin-8 dimer using a disulfide trap.
|
| |
Biochemistry,
45,
7882-7888.
|
|
|
|
|
|
|
O.K.Baryshnikova,
and
B.D.Sykes
(2006).
Backbone dynamics of SDF-1alpha determined by NMR: interpretation in the presence of monomer-dimer equilibrium.
|
| |
Protein Sci,
15,
2568-2578.
|
|
|
|
|
|
|
C.T.Veldkamp,
F.C.Peterson,
A.J.Pelzek,
and
B.F.Volkman
(2005).
The monomer-dimer equilibrium of stromal cell-derived factor-1 (CXCL 12) is altered by pH, phosphate, sulfate, and heparin.
|
| |
Protein Sci,
14,
1071-1081.
|
|
|
|
|
|
|
D.A.Davis,
K.E.Singer,
M.De La Luz Sierra,
M.Narazaki,
F.Yang,
H.M.Fales,
R.Yarchoan,
and
G.Tosato
(2005).
Identification of carboxypeptidase N as an enzyme responsible for C-terminal cleavage of stromal cell-derived factor-1alpha in the circulation.
|
| |
Blood,
105,
4561-4568.
|
|
|
|
|
|
|
F.Tsamis,
S.Gavrilov,
F.Kajumo,
C.Seibert,
S.Kuhmann,
T.Ketas,
A.Trkola,
A.Palani,
J.W.Clader,
J.R.Tagat,
S.McCombie,
B.Baroudy,
J.P.Moore,
T.P.Sakmar,
and
T.Dragic
(2003).
Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH-351125 and SCH-350581 inhibit human immunodeficiency virus type 1 entry.
|
| |
J Virol,
77,
5201-5208.
|
|
|
|
|
|
|
X.Huang,
J.Shen,
M.Cui,
L.Shen,
X.Luo,
K.Ling,
G.Pei,
H.Jiang,
and
K.Chen
(2003).
Molecular dynamics simulations on SDF-1alpha: binding with CXCR4 receptor.
|
| |
Biophys J,
84,
171-184.
|
|
|
|
|
|
|
E.J.Fernandez,
and
E.Lolis
(2002).
Structure, function, and inhibition of chemokines.
|
| |
Annu Rev Pharmacol Toxicol,
42,
469-499.
|
|
|
|
|
|
|
H.Lortat-Jacob,
A.Grosdidier,
and
A.Imberty
(2002).
Structural diversity of heparan sulfate binding domains in chemokines.
|
| |
Proc Natl Acad Sci U S A,
99,
1229-1234.
|
|
|
|
|
|
|
H.E.Broxmeyer
(2001).
Regulation of hematopoiesis by chemokine family members.
|
| |
Int J Hematol,
74,
9.
|
|
|
|
|
|
|
W.Shao,
E.Fernandez,
A.Sachpatzidis,
J.Wilken,
D.A.Thompson,
B.I.Schweitzer,
and
E.Lolis
(2001).
CCR2 and CCR5 receptor-binding properties of herpesvirus-8 vMIP-II based on sequence analysis and its solution structure.
|
| |
Eur J Biochem,
268,
2948-2959.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
Buyong,
J.Xiong,
J.Lubkowski,
and
R.Nussinov
(2000).
Homology modeling and molecular dynamics simulations of lymphotactin.
|
| |
Protein Sci,
9,
2192-2199.
|
|
|
|
|
|
|
N.Zhou,
Z.Luo,
J.Luo,
J.W.Hall,
and
Z.Huang
(2000).
A novel peptide antagonist of CXCR4 derived from the N-terminus of viral chemokine vMIP-II.
|
| |
Biochemistry,
39,
3782-3787.
|
|
|
|
|
|
|
P.E.Dawson,
and
S.B.Kent
(2000).
Synthesis of native proteins by chemical ligation.
|
| |
Annu Rev Biochem,
69,
923-960.
|
|
|
|
|
|
|
Y.Ohnishi,
T.Senda,
N.Nandhagopal,
K.Sugimoto,
T.Shioda,
Y.Nagal,
and
Y.Mitsui
(2000).
Crystal structure of recombinant native SDF-1alpha with additional mutagenesis studies: an attempt at a more comprehensive interpretation of accumulated structure-activity relationship data.
|
| |
J Interferon Cytokine Res,
20,
691-700.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
Z.Huang
(2000).
Structural chemistry and therapeutic intervention of protein-protein interactions in immune response, human immunodeficiency virus entry, and apoptosis.
|
| |
Pharmacol Ther,
86,
201-215.
|
|
|
|
|
|
|
Z.Luo,
X.Fan,
N.Zhou,
M.Hiraoka,
J.Luo,
H.Kaji,
and
Z.Huang
(2000).
Structure-function study and anti-HIV activity of synthetic peptide analogues derived from viral chemokine vMIP-II.
|
| |
Biochemistry,
39,
13545-13550.
|
|
|
|
|
|
|
A.C.Liwang,
Z.X.Wang,
Y.Sun,
S.C.Peiper,
and
P.J.Liwang
(1999).
The solution structure of the anti-HIV chemokine vMIP-II.
|
| |
Protein Sci,
8,
2270-2280.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
G.G.Kochendoerfer,
and
S.B.Kent
(1999).
Chemical protein synthesis.
|
| |
Curr Opin Chem Biol,
3,
665-671.
|
|
|
|
|
|
|
J.R.Sydor,
C.Herrmann,
S.B.Kent,
R.S.Goody,
and
M.Engelhard
(1999).
Design, total chemical synthesis, and binding properties of a [Leu-91-N1-methyl-7-azaTrp]Ras-binding domain of c-Raf-1.
|
| |
Proc Natl Acad Sci U S A,
96,
7865-7870.
|
|
|
|
|
|
|
N.J.Jordan,
G.Kolios,
S.E.Abbot,
M.A.Sinai,
D.A.Thompson,
K.Petraki,
and
J.Westwick
(1999).
Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells.
|
| |
J Clin Invest,
104,
1061-1069.
|
|
|
|
|
|
|
Y.Xu,
H.Tamamura,
R.Arakaki,
H.Nakashima,
X.Zhang,
N.Fujii,
T.Uchiyama,
and
T.Hattori
(1999).
Marked increase in anti-HIV activity, as well as inhibitory activity against HIV entry mediated by CXCR4, linked to enhancement of the binding ability of tachyplesin analogs to CXCR4.
|
| |
AIDS Res Hum Retroviruses,
15,
419-427.
|
|
|
|
|
|
|
J.Wilken,
and
S.B.Kent
(1998).
Chemical protein synthesis.
|
| |
Curr Opin Biotechnol,
9,
412-426.
|
|
|
|
|
|
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.
|
 |
Links
