PDBsum entry 5t6y

Immune system

PDB id: 5t6y

Contents

Protein chains

276 a.a.

99 a.a.

12 a.a.

Ligands

GOL ×3

ACT

Waters ×302

PDB id:

5t6y

Name:

Immune system

Title:

Hla-b 57:01 Presenting tstfedvkilaf

Structure:

Hla class i histocompatibility antigen, b-57 alpha chain. Chain: a. Fragment: unp residues 25-300. Synonym: bw-57,mhc class i antigen b 57. Engineered: yes. Beta-2-microglobulin. Chain: b. Fragment: unp residues 21-119. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-b, hlab. Expressed in: escherichia coli. Expression_system_taxid: 511693. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes. Synthetic construct.

Resolution:

1.76Å R-factor: 0.180 R-free: 0.219

Authors:

P.Pymm,J.Rossjohn,J.P.Vivian

Key ref:

P.Pymm et al. (2017). MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape. Nat Struct Biol, 24, 387-394. PubMed id: 28218747

Date:

02-Sep-16 Release date: 01-Mar-17

Protein chain

P01889  (1B07_HUMAN) -  HLA class I histocompatibility antigen, B alpha chain from Homo sapiens

Seq: 362 a.a.

Struc: 276 a.a.*

Protein chain

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

Seq: 119 a.a.

Struc: 99 a.a.

Protein chain

Q6YHU6  (THADA_HUMAN) -  tRNA (32-2'-O)-methyltransferase regulator THADA from Homo sapiens

Seq: 1953 a.a.

Struc: 12 a.a.

* PDB and UniProt seqs differ at 28 residue positions (black crosses)

Nat Struct Biol 24:387-394 (2017)

PubMed id: 28218747

MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape.

P.Pymm, P.T.Illing, S.H.Ramarathinam, G.M.O'Connor, V.A.Hughes, C.Hitchen, D.A.Price, B.K.Ho, D.W.McVicar, A.G.Brooks, A.W.Purcell, J.Rossjohn, J.P.Vivian.

ABSTRACT

Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove. The common escape mutant TSNLQEQIGW bound HLA-B*57:01 canonically, adopting a dramatically different conformation than the TW10 peptide. This affected recognition by killer cell immunoglobulin-like receptor (KIR) 3DL1 expressed on NK cells. We thus define a previously uncharacterized feature of the human leukocyte antigen class I (HLA-I) immunopeptidome that has implications for viral immune escape. We further suggest that recognition of the HLA-B*57:01-TW10 epitope is governed by a 'molecular tension' between the adaptive and innate immune systems.