Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structure of the human MHC-I peptide-loading complex.
Journal, issue, pages	Nature, Vol. 551, Issue 7681, Page 525-528, Year 2017
Publish date	Nov 23, 2017
Authors	Andreas Blees / Dovile Januliene / Tommy Hofmann / Nicole Koller / Carla Schmidt / Simon Trowitzsch / Arne Moeller / Robert Tampé /
PubMed Abstract	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response. The PLC coordinates ...The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response. The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules. After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells. Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin. The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex. Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy. Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I are centred around TAP in a pseudo-symmetric orientation. A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules. The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57. This arrangement allows tapasin to facilitate peptide editing by clamping MHC-I. The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I. Two lateral windows channel the antigenic peptides to MHC-I. Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I. Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
External links	Nature / PubMed:29107940
Methods	EM (single particle)
Resolution	5.8 - 9.9 Å
Structure data	EMDB-3904: CryoEM density map of the pseudosymmetric PLC editing modules Method: EM (single particle) / Resolution: 7.2 Å EMDB-3905: Cryo-EM density map of the human MHC-I peptide loading complex Method: EM (single particle) / Resolution: 9.9 Å 3906 6eny EMDB-3906: Cryo-EM density map of the human PLC editing module PDB-6eny: Structure of the human PLC editing module Method: EM (single particle) / Resolution: 5.8 Å
Source	homo sapiens (human) Human (human)
Keywords	IMMUNE SYSTEM / adaptive immunity / antigen processing / chaperone / MHC class I