A structural and molecular dynamics approach to understanding the peptide-receptive transition state of MHC-I molecules.
Mol Immunol
; 55(2): 123-5, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23200143
ABSTRACT
The mature conformation of major histocompatibility complex class I (MHC-I) proteins depends on the presence of bound peptides, permitting recognition at the cell surface by CD8(+) T lymphocytes. Newly synthesized MHC-I molecules in the endoplasmic reticulum are maintained in a peptide-receptive (PR) transition state by several chaperones until they are released concomitant with the loading of peptides. By determining the crystallographic structure of a region of an MHC-I molecule that is recognized by a unique monoclonal antibody and comparing this with docking and molecular dynamics simulations with the whole molecule, we demonstrate the movement of a hinged unit supporting the part of the binding groove that interacts with the amino terminal residues of the bound peptide. This unit contains a conserved 310 helix that flips from an exposed "open" position in the PR form to a "closed" position in the peptide-loaded (PL) mature molecule. These analyses indicate how this segment of the MHC-I molecule moves to help establish the A and B pockets critical for tight peptide binding and the stable structure required for antigen presentation and T cell recognition at the cell surface.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Histocompatibilidade Classe I
/
Linfócitos T CD8-Positivos
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Receptores de Reconhecimento de Padrão
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Simulação de Dinâmica Molecular
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article