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PDBsum entry 5knm
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Protein binding
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PDB id
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5knm
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Contents |
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276 a.a.
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101 a.a.
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187 a.a.
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References listed in PDB file
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Key reference
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Title
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Human leukocyte antigen f presents peptides and regulates immunity through interactions with nk cell receptors.
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Authors
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C.L.Dulberger,
C.P.Mcmurtrey,
A.Hölzemer,
K.E.Neu,
V.Liu,
A.M.Steinbach,
W.F.Garcia-Beltran,
M.Sulak,
B.Jabri,
V.J.Lynch,
M.Altfeld,
W.H.Hildebrand,
E.J.Adams.
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Ref.
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Immunity, 2017,
46,
1018.
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PubMed id
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Abstract
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Evidence is mounting that the major histocompatibility complex (MHC) molecule
HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy,
infection, and autoimmunity by signaling through NK cell receptors (NKRs). We
present structural, biochemical, and evolutionary analyses demonstrating that
HLA-F presents peptides of unconventional length dictated by a newly arisen
mutation (R62W) that has produced an open-ended groove accommodating
particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F
tetramers bound with human-derived peptides differentially stained leukocytes,
suggesting peptide-dependent engagement. Our in vitro studies confirm that NKRs
differentiate between peptide-bound and peptide-free HLA-F. The complex
structure of peptide-loaded β2m-HLA-F bound to the inhibitory LIR1
revealed similarities to high-affinity recognition of the viral MHC-I mimic UL18
and a docking strategy that relies on contacts with HLA-F as well as
β2m, thus precluding binding to HLA-F OCs. These findings provide a
biochemical framework to understand how HLA-F could regulate immunity via
interactions with NKRs.
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