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275 a.a.
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100 a.a.
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195 a.a.
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* Residue conservation analysis
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PDB id:
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Immune system
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Title:
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Crystal structure of the human natural killer cell inhibitory receptor kir2dl1 bound to its mhc ligand hla-cw4
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Structure:
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Hla class i histocompatibility antigen, cw-4 cw 0401 Alpha chain. Chain: a, e. Engineered: yes. Beta-2 microglobulin. Chain: b, f. Engineered: yes. Hla-cw4-specific peptide. Chain: c, g.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence has been obtained by pool sequencing of the peptides bound to hla-cw4 naturally..
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Biol. unit:
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Heptamer (from
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Resolution:
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2.80Å
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R-factor:
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0.213
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R-free:
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0.256
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Authors:
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Q.R.Fan,E.O.Long,D.C.Wiley
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Key ref:
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Q.R.Fan
et al.
(2001).
Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex.
Nat Immunol,
2,
452-460.
PubMed id:
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Date:
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10-May-01
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Release date:
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30-May-01
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PROCHECK
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Headers
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References
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P10321
(1C07_HUMAN) -
HLA class I histocompatibility antigen, C alpha chain from Homo sapiens
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Seq:
Struc:
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366 a.a.
275 a.a.*
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Nat Immunol
2:452-460
(2001)
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PubMed id:
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Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex.
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Q.R.Fan,
E.O.Long,
D.C.Wiley.
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ABSTRACT
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Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of
NK cells upon recognition of specific class I major histocompatibility complex
(MHC) molecules on target cells. We report here the crystal structure of the
inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound
to its class I MHC ligand, HLA-Cw4. The KIR2DL1-HLA-Cw4 interface exhibits
charge and shape complementarity. Specificity is mediated by a pocket in KIR2DL1
that hosts the Lys80 residue of HLA-Cw4. Many residues conserved in HLA-C and in
KIR2DL receptors make different interactions in KIR2DL1-HLA-Cw4 and in a
previously reported KIR2DL2-HLA-Cw3 complex. A dimeric aggregate of KIR-HLA-C
complexes was observed in one KIR2DL1-HLA-Cw4 crystal. Most of the amino acids
that differ between human and chimpanzee KIRs with HLA-C specificities form
solvent-accessible clusters outside the KIR-HLA interface, which suggests
undiscovered interactions by KIRs.
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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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K.S.Campbell,
and
A.K.Purdy
(2011).
Structure/function of human killer cell immunoglobulin-like receptors: lessons from polymorphisms, evolution, crystal structures and mutations.
|
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Immunology,
132,
315-325.
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|
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|
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M.E.Blais,
T.Dong,
and
S.Rowland-Jones
(2011).
HLA-C as a mediator of natural killer and T-cell activation: spectator or key player?
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Immunology,
133,
1-7.
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|
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M.G.Joyce,
P.Tran,
M.A.Zhuravleva,
J.Jaw,
M.Colonna,
and
P.D.Sun
(2011).
Crystal structure of human natural cytotoxicity receptor NKp30 and identification of its ligand binding site.
|
| |
Proc Natl Acad Sci U S A,
108,
6223-6228.
|
|
|
|
|
|
|
K.Köhler,
S.Xiong,
J.Brzostek,
M.Mehrabi,
P.Eissmann,
A.Harrison,
S.P.Cordoba,
S.Oddos,
V.Miloserdov,
K.Gould,
N.J.Burroughs,
P.A.van der Merwe,
and
D.M.Davis
(2010).
Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells.
|
| |
PLoS One,
5,
e15374.
|
|
|
|
|
|
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L.Abi-Rached,
A.K.Moesta,
R.Rajalingam,
L.A.Guethlein,
and
P.Parham
(2010).
Human-specific evolution and adaptation led to major qualitative differences in the variable receptors of human and chimpanzee natural killer cells.
|
| |
PLoS Genet,
6,
e1001192.
|
|
|
|
|
|
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N.G.Walpole,
L.Kjer-Nielsen,
L.Kostenko,
J.McCluskey,
A.G.Brooks,
J.Rossjohn,
and
C.S.Clements
(2010).
The structure and stability of the monomorphic HLA-G are influenced by the nature of the bound peptide.
|
| |
J Mol Biol,
397,
467-480.
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PDB codes:
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S.H.Hwang,
H.B.Oh,
S.E.Choi,
J.J.Seo,
J.H.Lee,
S.W.Cho,
J.M.Chae,
Y.S.Heo,
C.L.Chang,
and
E.Y.Lee
(2010).
Impact of amino acid substitution at residue 9 of HLA-A2 on the development of acute GVHD in Korean pediatric patients receiving unrelated hematopoietic stem cell transplantation.
|
| |
Transpl Int,
23,
1216-1222.
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S.Rajagopalan,
and
E.O.Long
(2010).
Antagonizing inhibition gets NK cells going.
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| |
Proc Natl Acad Sci U S A,
107,
10333-10334.
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|
|
|
|
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T.Gonen-Gross,
D.Goldman-Wohl,
B.Huppertz,
D.Lankry,
C.Greenfield,
S.Natanson-Yaron,
Y.Hamani,
R.Gilad,
S.Yagel,
and
O.Mandelboim
(2010).
Inhibitory NK receptor recognition of HLA-G: regulation by contact residues and by cell specific expression at the fetal-maternal interface.
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PLoS One,
5,
e8941.
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|
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|
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X.C.Li,
and
M.Raghavan
(2010).
Structure and function of major histocompatibility complex class I antigens.
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Curr Opin Organ Transplant,
15,
499-504.
|
|
|
|
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|
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D.Sharma,
K.Bastard,
L.A.Guethlein,
P.J.Norman,
N.Yawata,
M.Yawata,
M.Pando,
H.Thananchai,
T.Dong,
S.Rowland-Jones,
F.M.Brodsky,
and
P.Parham
(2009).
Dimorphic motifs in D0 and D1+D2 domains of killer cell Ig-like receptor 3DL1 combine to form receptors with high, moderate, and no avidity for the complex of a peptide derived from HIV and HLA-A*2402.
|
| |
J Immunol,
183,
4569-4582.
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|
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H.Thananchai,
T.Makadzange,
K.Maenaka,
K.Kuroki,
Y.Peng,
C.Conlon,
S.Rowland-Jones,
and
T.Dong
(2009).
Reciprocal recognition of an HLA-Cw4-restricted HIV-1 gp120 epitope by CD8+ T cells and NK cells.
|
| |
AIDS,
23,
189-193.
|
|
|
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|
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J.Pratschke,
D.Stauch,
and
K.Kotsch
(2009).
Role of NK and NKT cells in solid organ transplantation.
|
| |
Transpl Int,
22,
859-868.
|
|
|
|
|
|
|
P.Bowness,
S.Caplan,
and
M.Edidin
(2009).
MHC molecules lead many lives. Workshop on MHC Class I Molecules at the interface between Biology & Medicine.
|
| |
EMBO Rep,
10,
30-34.
|
|
|
|
|
|
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P.Kumar,
A.Vahedi-Faridi,
W.Saenger,
A.Ziegler,
and
B.Uchanska-Ziegler
(2009).
Conformational changes within the HLA-A1:MAGE-A1 complex induced by binding of a recombinant antibody fragment with TCR-like specificity.
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| |
Protein Sci,
18,
37-49.
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PDB code:
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R.Bari,
T.Bell,
W.H.Leung,
Q.P.Vong,
W.K.Chan,
N.Das Gupta,
M.Holladay,
B.Rooney,
and
W.Leung
(2009).
Significant functional heterogeneity among KIR2DL1 alleles and a pivotal role of arginine 245.
|
| |
Blood,
114,
5182-5190.
|
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|
|
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|
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T.Graef,
A.K.Moesta,
P.J.Norman,
L.Abi-Rached,
L.Vago,
A.M.Older Aguilar,
M.Gleimer,
J.A.Hammond,
L.A.Guethlein,
D.A.Bushnell,
P.J.Robinson,
and
P.Parham
(2009).
KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C.
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J Exp Med,
206,
2557-2572.
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PDB code:
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Y.Chen,
Y.Shi,
H.Cheng,
Y.Q.An,
and
G.F.Gao
(2009).
Structural immunology and crystallography help immunologists see the immune system in action: how T and NK cells touch their ligands.
|
| |
IUBMB Life,
61,
579-590.
|
|
|
|
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|
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Y.Li,
M.Hofmann,
Q.Wang,
L.Teng,
L.K.Chlewicki,
H.Pircher,
and
R.A.Mariuzza
(2009).
Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition.
|
| |
Immunity,
31,
35-46.
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PDB codes:
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A.M.Lazaro,
Y.Xiao,
K.Cao,
C.Masaberg,
L.Nichol,
J.Ng,
C.K.Hurley,
and
P.E.Posch
(2008).
Twenty-three novel alleles increase diversity at the HLA-C locus.
|
| |
Tissue Antigens,
71,
560-563.
|
|
|
|
|
|
|
E.J.Petrie,
C.S.Clements,
J.Lin,
L.C.Sullivan,
D.Johnson,
T.Huyton,
A.Heroux,
H.L.Hoare,
T.Beddoe,
H.H.Reid,
M.C.Wilce,
A.G.Brooks,
and
J.Rossjohn
(2008).
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence.
|
| |
J Exp Med,
205,
725-735.
|
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PDB code:
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H.Achdout,
I.Manaster,
and
O.Mandelboim
(2008).
Influenza virus infection augments NK cell inhibition through reorganization of major histocompatibility complex class I proteins.
|
| |
J Virol,
82,
8030-8037.
|
|
|
|
|
|
|
L.Sibilio,
A.Martayan,
A.Setini,
E.Lo Monaco,
E.Tremante,
R.H.Butler,
and
P.Giacomini
(2008).
A single bottleneck in HLA-C assembly.
|
| |
J Biol Chem,
283,
1267-1274.
|
|
|
|
|
|
|
M.P.Martin,
R.M.Single,
M.J.Wilson,
J.Trowsdale,
and
M.Carrington
(2008).
KIR haplotypes defined by segregation analysis in 59 Centre d'Etude Polymorphisme Humain (CEPH) families.
|
| |
Immunogenetics,
60,
767-774.
|
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|
|
|
|
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W.Held,
and
R.A.Mariuzza
(2008).
Cis interactions of immunoreceptors with MHC and non-MHC ligands.
|
| |
Nat Rev Immunol,
8,
269-278.
|
|
|
|
|
|
|
C.A.Velikovsky,
L.Deng,
L.K.Chlewicki,
M.M.Fernández,
V.Kumar,
and
R.A.Mariuzza
(2007).
Structure of natural killer receptor 2B4 bound to CD48 reveals basis for heterophilic recognition in signaling lymphocyte activation molecule family.
|
| |
Immunity,
27,
572-584.
|
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PDB codes:
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G.Yun,
J.Tolar,
A.K.Yerich,
S.G.Marsh,
J.Robinson,
H.Noreen,
B.R.Blazar,
and
J.S.Miller
(2007).
A novel method for KIR-ligand typing by pyrosequencing to predict NK cell alloreactivity.
|
| |
Clin Immunol,
123,
272-280.
|
|
|
|
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|
|
K.Kunert,
M.Seiler,
M.F.Mashreghi,
K.Klippert,
C.Schönemann,
K.Neumann,
J.Pratschke,
P.Reinke,
H.D.Volk,
and
K.Kotsch
(2007).
KIR/HLA ligand incompatibility in kidney transplantation.
|
| |
Transplantation,
84,
1527-1533.
|
|
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|
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|
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L.H.Hou,
N.K.Steiner,
M.Chen,
I.Belle,
J.Ng,
and
C.K.Hurley
(2007).
KIR2DL1 allelic diversity: four new alleles characterized in a bone marrow transplant population and three families.
|
| |
Tissue Antigens,
69,
250-254.
|
|
|
|
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|
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L.Luo,
Z.Du,
S.K.Sharma,
R.Cullen,
S.Spellman,
E.F.Reed,
and
R.Rajalingam
(2007).
Chain-terminating natural mutations affect the function of activating KIR receptors 3DS1 and 2DS3.
|
| |
Immunogenetics,
59,
779-792.
|
|
|
|
|
|
|
P.J.Norman,
L.Abi-Rached,
K.Gendzekhadze,
D.Korbel,
M.Gleimer,
D.Rowley,
D.Bruno,
C.V.Carrington,
D.Chandanayingyong,
Y.H.Chang,
C.Crespí,
G.Saruhan-Direskeneli,
P.A.Fraser,
K.Hameed,
G.Kamkamidze,
K.A.Koram,
Z.Layrisse,
N.Matamoros,
J.Milà,
M.H.Park,
R.M.Pitchappan,
D.D.Ramdath,
M.Y.Shiau,
H.A.Stephens,
S.Struik,
D.H.Verity,
R.W.Vaughan,
D.Tyan,
R.W.Davis,
E.M.Riley,
M.Ronaghi,
and
P.Parham
(2007).
Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans.
|
| |
Nat Genet,
39,
1092-1099.
|
|
|
|
|
|
|
Z.Du,
D.W.Gjertson,
E.F.Reed,
and
R.Rajalingam
(2007).
Receptor-ligand analyses define minimal killer cell Ig-like receptor (KIR) in humans.
|
| |
Immunogenetics,
59,
1.
|
|
|
|
|
|
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A.A.Bashirova,
M.P.Martin,
D.W.McVicar,
and
M.Carrington
(2006).
The killer immunoglobulin-like receptor gene cluster: tuning the genome for defense.
|
| |
Annu Rev Genomics Hum Genet,
7,
277-300.
|
|
|
|
|
|
|
C.Thilo,
P.Berglund,
S.E.Applequist,
J.W.Yewdell,
H.G.Ljunggren,
and
A.Achour
(2006).
Dissection of the interaction of the human cytomegalovirus-derived US2 protein with major histocompatibility complex class I molecules: prominent role of a single arginine residue in human leukocyte antigen-A2.
|
| |
J Biol Chem,
281,
8950-8957.
|
|
|
|
|
|
|
J.A.Campillo,
J.A.Martínez-Escribano,
M.Muro,
R.Moya-Quiles,
L.A.Marín,
O.Montes-Ares,
N.Guerra,
P.Sánchez-Pedreño,
J.F.Frías,
J.A.Lozano,
A.M.García-Alonso,
and
M.R.Alvarez-López
(2006).
HLA class I and class II frequencies in patients with cutaneous malignant melanoma from southeastern Spain: the role of HLA-C in disease prognosis.
|
| |
Immunogenetics,
57,
926-933.
|
|
|
|
|
|
|
L.Deng,
and
R.A.Mariuzza
(2006).
Structural basis for recognition of MHC and MHC-like ligands by natural killer cell receptors.
|
| |
Semin Immunol,
18,
159-166.
|
|
|
|
|
|
|
M.Shiroishi,
M.Kajikawa,
K.Kuroki,
T.Ose,
D.Kohda,
and
K.Maenaka
(2006).
Crystal structure of the human monocyte-activating receptor, "Group 2" leukocyte Ig-like receptor A5 (LILRA5/LIR9/ILT11).
|
| |
J Biol Chem,
281,
19536-19544.
|
|
|
PDB code:
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|
|
|
|
|
|
|
N.K.Steiner,
and
C.K.Hurley
(2006).
KIR3DL3 allelic diversity: six new alleles exhibit both conservative and non-conservative substitutions.
|
| |
Tissue Antigens,
67,
277-283.
|
|
|
|
|
|
|
G.B.Stewart-Jones,
K.di Gleria,
S.Kollnberger,
A.J.McMichael,
E.Y.Jones,
and
P.Bowness
(2005).
Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA-B*2705.
|
| |
Eur J Immunol,
35,
341-351.
|
|
|
PDB codes:
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|
|
|
|
|
|
|
J.A.López de Castro
(2005).
HLA-B27: portraying immunodominant viral epitopes.
|
| |
Eur J Immunol,
35,
336-340.
|
|
|
|
|
|
|
K.L.Hershberger,
J.Kurian,
B.T.Korber,
and
N.L.Letvin
(2005).
Killer cell immunoglobulin-like receptors (KIR) of the African-origin sabaeus monkey: evidence for recombination events in the evolution of KIR.
|
| |
Eur J Immunol,
35,
922-935.
|
|
|
|
|
|
|
M.Hülsmeyer,
P.Chames,
R.C.Hillig,
R.L.Stanfield,
G.Held,
P.G.Coulie,
C.Alings,
G.Wille,
W.Saenger,
B.Uchanska-Ziegler,
H.R.Hoogenboom,
and
A.Ziegler
(2005).
A major histocompatibility complex-peptide-restricted antibody and t cell receptor molecules recognize their target by distinct binding modes: crystal structure of human leukocyte antigen (HLA)-A1-MAGE-A1 in complex with FAB-HYB3.
|
| |
J Biol Chem,
280,
2972-2980.
|
|
|
PDB code:
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|
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|
|
N.Gómez-Lozano,
E.Estefanía,
F.Williams,
I.Halfpenny,
D.Middleton,
R.Solís,
and
C.Vilches
(2005).
The silent KIR3DP1 gene (CD158c) is transcribed and might encode a secreted receptor in a minority of humans, in whom the KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1 genes are duplicated.
|
| |
Eur J Immunol,
35,
16-24.
|
|
|
|
|
|
|
S.H.Hwang,
C.H.Cha,
O.J.Kwon,
Y.S.Heo,
S.S.Hur,
M.N.Lee,
and
H.B.Oh
(2005).
Novel HLA-Cw*06 allele, Cw*0612, identified by sequence-based typing.
|
| |
Tissue Antigens,
66,
330-331.
|
|
|
|
|
|
|
C.Lecut,
V.Arocas,
H.Ulrichts,
A.Elbaz,
J.L.Villeval,
J.J.Lacapère,
H.Deckmyn,
and
M.Jandrot-Perrus
(2004).
Identification of residues within human glycoprotein VI involved in the binding to collagen: evidence for the existence of distinct binding sites.
|
| |
J Biol Chem,
279,
52293-52299.
|
|
|
|
|
|
|
S.E.Hiby,
J.J.Walker,
K.M.O'shaughnessy,
C.W.Redman,
M.Carrington,
J.Trowsdale,
and
A.Moffett
(2004).
Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success.
|
| |
J Exp Med,
200,
957-965.
|
|
|
|
|
|
|
C.E.Foster,
M.Colonna,
and
P.D.Sun
(2003).
Crystal structure of the human natural killer (NK) cell activating receptor NKp46 reveals structural relationship to other leukocyte receptor complex immunoreceptors.
|
| |
J Biol Chem,
278,
46081-46086.
|
|
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PDB code:
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M.Shiroishi,
K.Tsumoto,
K.Amano,
Y.Shirakihara,
M.Colonna,
V.M.Braud,
D.S.Allan,
A.Makadzange,
S.Rowland-Jones,
B.Willcox,
E.Y.Jones,
P.A.van der Merwe,
I.Kumagai,
and
K.Maenaka
(2003).
Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G.
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Proc Natl Acad Sci U S A,
100,
8856-8861.
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S.Radaev,
and
P.D.Sun
(2003).
Structure and function of natural killer cell surface receptors.
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Annu Rev Biophys Biomol Struct,
32,
93.
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V.Hofmeister,
and
E.H.Weiss
(2003).
HLA-G modulates immune responses by diverse receptor interactions.
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Semin Cancer Biol,
13,
317-323.
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X.Saulquin,
L.N.Gastinel,
and
E.Vivier
(2003).
Crystal structure of the human natural killer cell activating receptor KIR2DS2 (CD158j).
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J Exp Med,
197,
933-938.
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PDB code:
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B.E.Willcox,
L.M.Thomas,
T.L.Chapman,
A.P.Heikema,
A.P.West,
and
P.J.Bjorkman
(2002).
Crystal structure of LIR-2 (ILT4) at 1.8 A: differences from LIR-1 (ILT2) in regions implicated in the binding of the Human Cytomegalovirus class I MHC homolog UL18.
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BMC Struct Biol,
2,
6.
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PDB code:
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C.Vilches,
and
P.Parham
(2002).
KIR: diverse, rapidly evolving receptors of innate and adaptive immunity.
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Annu Rev Immunol,
20,
217-251.
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E.O.Long,
and
S.Rajagopalan
(2002).
Stress signals activate natural killer cells.
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J Exp Med,
196,
1399-1402.
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F.E.McCann,
K.Suhling,
L.M.Carlin,
K.Eleme,
S.B.Taner,
K.Yanagi,
B.Vanherberghen,
P.M.French,
and
D.M.Davis
(2002).
Imaging immune surveillance by T cells and NK cells.
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| |
Immunol Rev,
189,
179-192.
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J.S.Gatot,
I.Callebaut,
C.Van Lint,
D.Demonté,
P.Kerkhofs,
D.Portetelle,
A.Burny,
L.Willems,
and
R.Kettmann
(2002).
Bovine leukemia virus SU protein interacts with zinc, and mutations within two interacting regions differently affect viral fusion and infectivity in vivo.
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| |
J Virol,
76,
7956-7967.
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K.C.Hsu,
S.Chida,
D.E.Geraghty,
and
B.Dupont
(2002).
The killer cell immunoglobulin-like receptor (KIR) genomic region: gene-order, haplotypes and allelic polymorphism.
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| |
Immunol Rev,
190,
40-52.
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K.Natarajan,
N.Dimasi,
J.Wang,
R.A.Mariuzza,
and
D.H.Margulies
(2002).
Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination.
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| |
Annu Rev Immunol,
20,
853-885.
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L.D.Maxwell,
A.Wallace,
D.Middleton,
and
M.D.Curran
(2002).
A common KIR2DS4 deletion variant in the human that predicts a soluble KIR molecule analogous to the KIR1D molecule observed in the rhesus monkey.
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Tissue Antigens,
60,
254-258.
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S.I.Khakoo,
R.Geller,
S.Shin,
J.A.Jenkins,
and
P.Parham
(2002).
The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer.
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J Exp Med,
196,
911-921.
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B.E.Gewurz,
R.Gaudet,
D.Tortorella,
E.W.Wang,
H.L.Ploegh,
and
D.C.Wiley
(2001).
Antigen presentation subverted: Structure of the human cytomegalovirus protein US2 bound to the class I molecule HLA-A2.
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Proc Natl Acad Sci U S A,
98,
6794-6799.
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PDB code:
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B.E.Gewurz,
R.Gaudet,
D.Tortorella,
E.W.Wang,
and
H.L.Ploegh
(2001).
Virus subversion of immunity: a structural perspective.
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| |
Curr Opin Immunol,
13,
442-450.
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J.Trowsdale
(2001).
Genetic and functional relationships between MHC and NK receptor genes.
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Immunity,
15,
363-374.
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L.M.Carlin,
K.Eleme,
F.E.McCann,
and
D.M.Davis
(2001).
Intercellular transfer and supramolecular organization of human leukocyte antigen C at inhibitory natural killer cell immune synapses.
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J Exp Med,
194,
1507-1517.
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S.Radaev,
B.Rostro,
A.G.Brooks,
M.Colonna,
and
P.D.Sun
(2001).
Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3.
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Immunity,
15,
1039-1049.
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PDB code:
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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
codes are
shown on the right.
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