6C9D

Crystal structure of KA1-autoinhibited MARK1 kinase

Summary for 6C9D

• Entry DOI: 10.2210/pdb6c9d/pdb
• Descriptor: Serine/threonine-protein kinase MARK1,Serine/threonine-protein kinase MARK1 (2 entities in total)
• Functional Keywords: kinase, camkl, ka1 domain, autoinhibition, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 105873.43

Authors

Emptage, R.P.,Marmorstein, R. (deposition date: 2018-01-26, release date: 2018-07-11, Last modification date: 2023-10-04)

Primary citation

Emptage, R.P.,Lemmon, M.A.,Ferguson, K.M.,Marmorstein, R.
Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain.
Structure, 26:1137-, 2018

PubMed Abstract: 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.

PubMed: 30099988
DOI: 10.1016/j.str.2018.05.008

Experimental method

X-RAY DIFFRACTION (2.499 Å)