PDBsum entry 6tdo

Immune system

PDB id: 6tdo

Contents

Protein chains

274 a.a.

99 a.a.

Ligands

GLY-MET

GOL ×2

Waters ×522

PDB id:

6tdo

Name:

Immune system

Title:

Crystal structure of the disulfide engineered hla-a0201 molecule in complex with one gm dipeptide in the a pocket.

Structure:

Mhc class i antigen. Chain: a. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes

Source:

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

Resolution:

1.65Å R-factor: 0.188 R-free: 0.224

Authors:

R.Anjanappa,M.Garcia Alai,S.Springer,R.Meijers

Key ref:

R.Anjanappa et al. (2020). Structures of peptide-free and partially loaded MHC class I molecules reveal mechanisms of peptide selection. Nat Commun, 11, 1314. PubMed id: 32161266 DOI: 10.1038/s41467-020-14862-4

Date:

09-Nov-19 Release date: 25-Mar-20

Protein chain

F6IQS1  (F6IQS1_HUMAN) -  MHC class I antigen (Fragment) from Homo sapiens

Seq: 337 a.a.

Struc: 274 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 3 residue positions (black crosses)

DOI no: 10.1038/s41467-020-14862-4

Nat Commun 11:1314 (2020)

PubMed id: 32161266

Structures of peptide-free and partially loaded MHC class I molecules reveal mechanisms of peptide selection.

R.Anjanappa, M.Garcia-Alai, J.D.Kopicki, J.Lockhauserbäumer, M.Aboelmagd, J.Hinrichs, I.M.Nemtanu, C.Uetrecht, M.Zacharias, S.Springer, R.Meijers.

ABSTRACT

Major Histocompatibility Complex (MHC) class I molecules selectively bind peptides for presentation to cytotoxic T cells. The peptide-free state of these molecules is not well understood. Here, we characterize a disulfide-stabilized version of the human class I molecule HLA-A*02:01 that is stable in the absence of peptide and can readily exchange cognate peptides. We present X-ray crystal structures of the peptide-free state of HLA-A*02:01, together with structures that have dipeptides bound in the A and F pockets. These structural snapshots reveal that the amino acid side chains lining the binding pockets switch in a coordinated fashion between a peptide-free unlocked state and a peptide-bound locked state. Molecular dynamics simulations suggest that the opening and closing of the F pocket affects peptide ligand conformations in adjacent binding pockets. We propose that peptide binding is co-determined by synergy between the binding pockets of the MHC molecule.