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PDBsum entry 6c9d
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References listed in PDB file
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Key reference
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Title
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Structural basis for mark1 kinase autoinhibition by its ka1 domain.
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Authors
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R.P.Emptage,
M.A.Lemmon,
K.M.Ferguson,
R.Marmorstein.
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Ref.
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Structure, 2018,
26,
1137.
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PubMed id
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Abstract
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The kinase associated-1 (KA1) domain is found at the C-terminus of multiple
Ser/Thr protein kinases from yeast to humans, and has been assigned
autoinhibitory, membrane-binding, and substrate-targeting roles. Here, we report
the crystal structure of the MARK1 kinase/UBA domain bound to its autoinhibitory
KA1 domain, revealing an unexpected interface at the αD helix and contacts with
both the N- and C-lobes of the kinase domain. We confirm the binding interface
location in kinetic studies of variants mutated on the kinase domain surface.
Together with other MARK kinase structures, the data implicate that the KA1
domain blocks peptide substrate binding. The structure highlights the
kinase-specific autoinhibitory binding modes of different KA1 domains, and
provides potential new avenues by which to intervene therapeutically in
Alzheimer's disease and cancers in which MARK1 or related kinases are implicated.
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