PDBsum entry 5fa3

Immune system

PDB id: 5fa3

Contents

Protein chains

273 a.a.

99 a.a.

Ligands

GLY-LEU-LEU-PRO-GLU-LEU-PRO-ALA-VAL

GOL ×3

Waters ×257

PDB id:

5fa3

Name:

Immune system

Title:

Structure of hla-a2:01 with peptide g9v

Structure:

Hla class i histocompatibility antigen, a-2 alpha chain. Chain: a. Synonym: mhc class i antigen a 2. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes. G9v. Chain: c.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-a, hlaa. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes. Toxoplasma gondii.

Resolution:

1.86Å R-factor: 0.211 R-free: 0.235

Authors:

D.M.Zajonc,S.G.Remesh

Key ref:

S.G.Remesh et al. (2017). Unconventional Peptide Presentation by Major Histocompatibility Complex (MHC) Class I Allele HLA-A*02:01: BREAKING CONFINEMENT. J Biol Chem, 292, 5262-5270. PubMed id: 28179428

Date:

10-Dec-15 Release date: 21-Dec-16

Protein chain

P04439  (1A03_HUMAN) -  HLA class I histocompatibility antigen, A alpha chain from Homo sapiens

Seq: 365 a.a.

Struc: 273 a.a.*

Protein chain

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

Seq: 119 a.a.

Struc: 99 a.a.

* PDB and UniProt seqs differ at 19 residue positions (black crosses)

J Biol Chem 292:5262-5270 (2017)

PubMed id: 28179428

Unconventional Peptide Presentation by Major Histocompatibility Complex (MHC) Class I Allele HLA-A*02:01: BREAKING CONFINEMENT.

S.G.Remesh, M.Andreatta, G.Ying, T.Kaever, M.Nielsen, C.McMurtrey, W.Hildebrand, B.Peters, D.M.Zajonc.

ABSTRACT

Peptide antigen presentation by major histocompatibility complex (MHC) class I proteins initiates CD8⁺ T cell-mediated immunity against pathogens and cancers. MHC I molecules typically bind peptides with 9 amino acids in length with both ends tucked inside the major A and F binding pockets. It has been known for a while that longer peptides can also bind by either bulging out of the groove in the middle of the peptide or by binding in a zigzag fashion inside the groove. In a recent study, we identified an alternative binding conformation of naturally occurring peptides from Toxoplasma gondii bound by HLA-A*02:01. These peptides were extended at the C terminus (PΩ) and contained charged amino acids not more than 3 residues after the anchor amino acid at PΩ, which enabled them to open the F pocket and expose their C-terminal extension into the solvent. Here, we show that the mechanism of F pocket opening is dictated by the charge of the first charged amino acid found within the extension. Although positively charged amino acids result in the Tyr-84 swing, amino acids that are negatively charged induce a not previously described Lys-146 lift. Furthermore, we demonstrate that the peptides with alternative binding modes have properties that fit very poorly to the conventional MHC class I pathway and suggest they are presented via alternative means, potentially including cross-presentation via the MHC class II pathway.