PDBsum entry 2ypl

Immune system/viral protein

PDB id: 2ypl

Contents

Protein chains

274 a.a.

99 a.a.

11 a.a.

199 a.a.

238 a.a.

Waters ×195

PDB id:

2ypl

Name:

Immune system/viral protein

Title:

Structural features underlying t-cell receptor sensitivity to concealed mhc class i micropolymorphisms

Structure:

Hla class i histocompatibility antigen, b-57 alpha chain. Chain: a. Fragment: residues 25-298. Synonym: bw-57, mhc class i antigen b 57, Hla-b5703. Engineered: yes. Beta-2-microglobulin. Chain: b. Synonym: beta-2-microglobulin form pi 5.3. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Human immunodeficiency virus. Organism_taxid: 12721.

Resolution:

2.40Å R-factor: 0.224 R-free: 0.277

Authors:

G.B.Stewart-Jones,P.Simpson,P.A.Van Der Merwe,P.Easterbrook, A.J.Mcmichael,S.L.Rowland-Jones,E.Y.Jones,G.M.Gillespie

Key ref:

G.B.Stewart-Jones et al. (2012). Structural features underlying T-cell receptor sensitivity to concealed MHC class I micropolymorphisms. Proc Natl Acad Sci U S A, 109, E3483. PubMed id: 23161907

Date:

30-Oct-12 Release date: 28-Nov-12

Protein chain

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

Seq: 362 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.

Protein chain

Q70XD7  (Q70XD7_HV1) -  Gag polyprotein from Human immunodeficiency virus type 1

Seq: 1499 a.a.

Struc: 11 a.a.

Protein chain

No UniProt id for this chain

Struc: 199 a.a.

Protein chain

No UniProt id for this chain

Struc: 238 a.a.

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

Enzyme reactions

• Enzyme class 2: Chain C: E.C.3.1.13.2 - exoribonuclease H.
• Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
• Enzyme class 3: Chain C: E.C.3.1.26.13 - retroviral ribonuclease H.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Proc Natl Acad Sci U S A 109:E3483 (2012)

PubMed id: 23161907

Structural features underlying T-cell receptor sensitivity to concealed MHC class I micropolymorphisms.

G.B.Stewart-Jones, P.Simpson, P.A.van der Merwe, P.Easterbrook, A.J.McMichael, S.L.Rowland-Jones, E.Y.Jones, G.M.Gillespie.

ABSTRACT

Polymorphic differences distinguishing MHC class I subtypes often permit the presentation of shared epitopes in conformationally identical formats but can affect T-cell repertoire selection, differentially impacting autoimmune susceptibilities and viral clearance in vivo. The molecular mechanisms underlying this effect are not well understood. We performed structural, thermodynamic, and functional analyses of a conserved T-cell receptor (TCR) which is frequently expanded in response to a HIV-1 epitope when presented by HLA-B*5701 but is not selected by HLA-B*5703, which differs from HLA-B*5701 by two concealed polymorphisms. Our findings illustrate that although both HLA-B*57 subtypes display the epitope in structurally conserved formats, the impact of their polymorphic differences occurs directly as a consequence of TCR ligation, primarily because of peptide adjustments required for TCR binding, which involves the interplay of polymorphic residues and water molecules. These minor differences culminate in subtype-specific differential TCR-binding kinetics and cellular function. Our data demonstrate a potential mechanism whereby the most subtle MHC class I micropolymorphisms can influence TCR use and highlight their implications for disease outcomes.