4GUP

Structure of MHC-class I related molecule MR1

Summary for 4GUP

• Entry DOI: 10.2210/pdb4gup/pdb
• Descriptor: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, 2-amino-4-oxo-3,4-dihydropteridine-6-carbaldehyde, ... (5 entities in total)
• Functional Keywords: mhc class i-related protein, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass membrane protein; Extracellular side. Isoform 4: Secreted: Q95460; Secreted: P61769
• Total number of polymer chains: 4
• Total formula weight: 87432.38

Authors

Patel, O.,Le Nours, J.,Rossjohn, J. (deposition date: 2012-08-29, release date: 2012-10-17, Last modification date: 2024-10-30)

Primary citation

Kjer-Nielsen, L.,Patel, O.,Corbett, A.J.,Le Nours, J.,Meehan, B.,Liu, L.,Bhati, M.,Chen, Z.,Kostenko, L.,Reantragoon, R.,Williamson, N.A.,Purcell, A.W.,Dudek, N.L.,McConville, M.J.,O'Hair, R.A.J.,Khairallah, G.N.,Godfrey, D.I.,Fairlie, D.P.,Rossjohn, J.,McCluskey, J.
MR1 presents microbial vitamin B metabolites to MAIT cells
Nature, 491:717-723, 2012

PubMed Abstract: Antigen-presenting molecules, encoded by the major histocompatibility complex (MHC) and CD1 family, bind peptide- and lipid-based antigens, respectively, for recognition by T cells. Mucosal-associated invariant T (MAIT) cells are an abundant population of innate-like T cells in humans that are activated by an antigen(s) bound to the MHC class I-like molecule MR1. Although the identity of MR1-restricted antigen(s) is unknown, it is present in numerous bacteria and yeast. Here we show that the structure and chemistry within the antigen-binding cleft of MR1 is distinct from the MHC and CD1 families. MR1 is ideally suited to bind ligands originating from vitamin metabolites. The structure of MR1 in complex with 6-formyl pterin, a folic acid (vitamin B9) metabolite, shows the pterin ring sequestered within MR1. Furthermore, we characterize related MR1-restricted vitamin derivatives, originating from the bacterial riboflavin (vitamin B2) biosynthetic pathway, which specifically and potently activate MAIT cells. Accordingly, we show that metabolites of vitamin B represent a class of antigen that are presented by MR1 for MAIT-cell immunosurveillance. As many vitamin biosynthetic pathways are unique to bacteria and yeast, our data suggest that MAIT cells use these metabolites to detect microbial infection.

PubMed: 23051753
DOI: 10.1038/nature11605

Experimental method

X-RAY DIFFRACTION (3.2 Å)