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Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complex
Abstract
The covalent conjugation of a 14-carbon saturated fatty acid (myristic acid) to the amino-terminal glycine residue is critical for some viral proteins to function. This protein lipidation modification, termed N-myristoylation, is targeted by host cytotoxic T lymphocytes (CTLs) that specifically recognize N-myristoylated short peptides; however, the molecular mechanisms underlying lipopeptide antigen (Ag) presentation remain elusive. Here we show that a primate major histocompatibility complex (MHC) class I-encoded protein is capable of binding N-myristoylated 5-mer peptides and presenting them to specific CTLs. A high-resolution X-ray crystallographic analysis of the MHC class I:lipopeptide complex reveals an Ag-binding groove that is elaborately constructed to bind N-myristoylated short peptides rather than prototypic 9-mer peptides. The identification of lipopeptide-specific, MHC class I-restricted CTLs indicates that the widely accepted concept of MHC class I-mediated presentation of long peptides to CTLs may need some modifications to incorporate a novel MHC class I function of lipopeptide Ag presentation.
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Metadata
- Authors
- Morita, D., Yamamoto, Y., Mizutani, T., Ishikawa, T., Suzuki, J., Igarashi, T., Mori, N., Shiina, T., Inoko, H., Fujita, H., Iwai, K., Tanaka, Y., Mikami, B., & Sugita, M.
- Venue
- Nature Communications
- Published
- 2016-01-13
- Volume
- 7
- Issue
- 1
- ISSN
- 2041-1723
- Cited by
- 20
- References
- 2
- Language
- en
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- Morita, D., Yamamoto, Y., Mizutani, T., Ishikawa, T., Suzuki, J., Igarashi, T., Mori, N., Shiina, T., Inoko, H., Fujita, H., Iwai, K., Tanaka, Y., Mikami, B., & Sugita, M. (2016). Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complex. Nature Communications. https://doi.org/10.1038/ncomms10356