7M72

MHC-like protein complex structure

Summary for 7M72

• Entry DOI: 10.2210/pdb7m72/pdb
• Descriptor: Antigen-presenting glycoprotein CD1d1, Beta-2-microglobulin, NKT Valpha14 (Mouse)-2C12 TCR,Human T-cell receptor sp3.4 alpha chain, ... (9 entities in total)
• Functional Keywords: mhc-like protein, cd1d1 antigen presenting molecule, lipid binding protein complex, lipid binding protein, lipid binding protein-immune system complex, lipid binding protein/immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 4
• Total formula weight: 98469.13

Authors

Thirunavukkarasu, P.,Le Nours, J.,Rossjohn, J. (deposition date: 2021-03-26, release date: 2021-11-10, Last modification date: 2024-10-16)

Primary citation

Oh, S.F.,Praveena, T.,Song, H.,Yoo, J.S.,Jung, D.J.,Erturk-Hasdemir, D.,Hwang, Y.S.,Lee, C.C.,Le Nours, J.,Kim, H.,Lee, J.,Blumberg, R.S.,Rossjohn, J.,Park, S.B.,Kasper, D.L.
Host immunomodulatory lipids created by symbionts from dietary amino acids.
Nature, 600:302-307, 2021

PubMed Abstract: Small molecules derived from symbiotic microbiota critically contribute to intestinal immune maturation and regulation. However, little is known about the molecular mechanisms that control immune development in the host-microbiota environment. Here, using a targeted lipidomic analysis and synthetic approach, we carried out a multifaceted investigation of immunomodulatory α-galactosylceramides from the human symbiont Bacteroides fragilis (BfaGCs). The characteristic terminal branching of BfaGCs is the result of incorporation of branched-chain amino acids taken up in the host gut by B. fragilis. A B. fragilis knockout strain that cannot metabolize branched-chain amino acids showed reduced branching in BfaGCs, and mice monocolonized with this mutant strain had impaired colonic natural killer T (NKT) cell regulation, implying structure-specific immunomodulatory activity. The sphinganine chain branching of BfaGCs is a critical determinant of NKT cell activation, which induces specific immunomodulatory gene expression signatures and effector functions. Co-crystal structure and affinity analyses of CD1d-BfaGC-NKT cell receptor complexes confirmed the interaction of BfaGCs as CD1d-restricted ligands. We present a structural and molecular-level paradigm of immunomodulatory control by interactions of endobiotic metabolites with diet, microbiota and the immune system.

PubMed: 34759313
DOI: 10.1038/s41586-021-04083-0

Experimental method

X-RAY DIFFRACTION (2.4 Å)