PDBsum entry 5knm

Protein binding

PDB id: 5knm

Contents

Protein chains

276 a.a.

101 a.a.

187 a.a.

Ligands

ILE-LEU-ARG-TRP-GLU-GLN

NAG

PDB id:

5knm

Name:

Protein binding

Title:

Human leukocyte antigen f (hla-f) presents peptides and regulates immunity through interactions with nk-cell receptors

Structure:

Cdna flj39643 fis, clone smint2004023, highly similar to hla class i histocompatibility antigen, alphachain f. Chain: a. Fragment: unp residues 22-305. Engineered: yes. Beta-2-microglobulin. Chain: b. Fragment: unp rrsidues 21-119. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell: high five. Gene: b2m, cdabp0092, hdcma22p. Gene: lilrb1, ilt2, lir1, mir7. Trichoplusia ni.

Resolution:

3.30Å R-factor: 0.305 R-free: 0.326

Authors:

C.L.Dulberger,E.J.Adams

Key ref:

C.L.Dulberger et al. (2017). Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors. Immunity, 46, 1018. PubMed id: 28636952

Date:

28-Jun-16 Release date: 14-Jun-17

Protein chain

P30511  (HLAF_HUMAN) -  HLA class I histocompatibility antigen, alpha chain F from Homo sapiens

Seq: 346 a.a.

Struc: 276 a.a.*

Protein chain

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 101 a.a.*

Protein chain

Q8NHL6  (LIRB1_HUMAN) -  Leukocyte immunoglobulin-like receptor subfamily B member 1 from Homo sapiens

Seq: 650 a.a.

Struc: 187 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Immunity 46:1018 (2017)

PubMed id: 28636952

Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors.

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.

ABSTRACT

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.