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PDBsum entry 5fn8
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References listed in PDB file
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Key reference
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Title
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Initiation of t cell signaling by cd45 segregation at 'Close contacts'.
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Authors
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V.T.Chang,
R.A.Fernandes,
K.A.Ganzinger,
S.F.Lee,
C.Siebold,
J.Mccoll,
P.Jönsson,
M.Palayret,
K.Harlos,
C.H.Coles,
E.Y.Jones,
Y.Lui,
E.Huang,
R.J.Gilbert,
D.Klenerman,
A.R.Aricescu,
S.J.Davis.
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Ref.
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Nat Immunol, 2016,
17,
574-582.
[DOI no: ]
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PubMed id
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Abstract
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It has been proposed that the local segregation of kinases and the tyrosine
phosphatase CD45 underpins T cell antigen receptor (TCR) triggering, but how
such segregation occurs and whether it can initiate signaling is unclear. Using
structural and biophysical analysis, we show that the extracellular region of
CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes,
implying that sites of TCR-ligand engagement would sterically exclude CD45. We
also show that the formation of 'close contacts', new structures characterized
by spontaneous CD45 and kinase segregation at the submicron-scale, initiates
signaling even when TCR ligands are absent. Our work reveals the structural
basis for, and the potent signaling effects of, local CD45 and kinase
segregation. TCR ligands have the potential to heighten signaling simply by
holding receptors in close contacts.
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