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PDBsum entry 6tdo
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Immune system
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PDB id
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6tdo
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References listed in PDB file
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Key reference
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Title
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Structures of peptide-Free and partially loaded mhc class i molecules reveal mechanisms of peptide selection.
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Authors
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R.Anjanappa,
M.Garcia-Alai,
J.D.Kopicki,
J.Lockhauserbäumer,
M.Aboelmagd,
J.Hinrichs,
I.M.Nemtanu,
C.Uetrecht,
M.Zacharias,
S.Springer,
R.Meijers.
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Ref.
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Nat Commun, 2020,
11,
1314.
[DOI no: ]
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PubMed id
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Abstract
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Major Histocompatibility Complex (MHC) class I molecules selectively bind
peptides for presentation to cytotoxic T cells. The peptide-free state of these
molecules is not well understood. Here, we characterize a disulfide-stabilized
version of the human class I molecule HLA-A*02:01 that is stable in the absence
of peptide and can readily exchange cognate peptides. We present X-ray crystal
structures of the peptide-free state of HLA-A*02:01, together with structures
that have dipeptides bound in the A and F pockets. These structural snapshots
reveal that the amino acid side chains lining the binding pockets switch in a
coordinated fashion between a peptide-free unlocked state and a peptide-bound
locked state. Molecular dynamics simulations suggest that the opening and
closing of the F pocket affects peptide ligand conformations in adjacent binding
pockets. We propose that peptide binding is co-determined by synergy between the
binding pockets of the MHC molecule.
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