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PDBsum entry 4o2e
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Immune system
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PDB id
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4o2e
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References listed in PDB file
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Key reference
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Title
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Nα-Terminal acetylation for t cell recognition: molecular basis of mhc class i-Restricted nα-Acetylpeptide presentation.
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Authors
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M.Sun,
J.Liu,
J.Qi,
B.Tefsen,
Y.Shi,
J.Yan,
G.F.Gao.
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Ref.
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J Immunol, 2014,
192,
5509-5519.
[DOI no: ]
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PubMed id
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Abstract
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As one of the most common posttranslational modifications (PTMs) of eukaryotic
proteins, N(α)-terminal acetylation (Nt-acetylation) generates a class of
N(α)-acetylpeptides that are known to be presented by MHC class I at the cell
surface. Although such PTM plays a pivotal role in adjusting proteolysis, the
molecular basis for the presentation and T cell recognition of
N(α)-acetylpeptides remains largely unknown. In this study, we determined a
high-resolution crystallographic structure of HLA (HLA)-B*3901 complexed with an
N(α)-acetylpeptide derived from natural cellular processing, also in comparison
with the unmodified-peptide complex. Unlike the α-amino-free P1 residues of
unmodified peptide, of which the α-amino group inserts into pocket A of the
Ag-binding groove, the N(α)-linked acetyl of the acetylated P1-Ser protrudes
out of the groove for T cell recognition. Moreover, the Nt-acetylation not only
alters the conformation of the peptide but also switches the residues in the
α1-helix of HLA-B*3901, which may impact the T cell engagement. The
thermostability measurements of complexes between N(α)-acetylpeptides and a
series of MHC class I molecules derived from different species reveal reduced
stability. Our findings provide the insight into the mode of
N(α)-acetylpeptide-specific presentation by classical MHC class I molecules and
shed light on the potential of acetylepitope-based immune intervene and vaccine
development.
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