A Mechanism for Tunable Autoinhibition in the Structure of a Human Ca2+/Calmodulin- Dependent Kinase II Holoenzyme | Zendy

Luke H. Chao | Zendy; Margaret M. Stratton | Zendy; IlHyung Lee | Zendy; Oren S. Rosenberg | Zendy; Joshua Levitz | Zendy; Daniel J. Mandell | Zendy; Tanja Kortemme | Zendy; Jay T. Groves | Zendy; Howard Schulman | Zendy; John Kuriyan | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

A Mechanism for Tunable Autoinhibition in the Structure of a Human Ca2+/Calmodulin- Dependent Kinase II Holoenzyme

Author(s) -

Luke H. Chao,

Margaret M. Stratton,

IlHyung Lee,

Oren S. Rosenberg,

Joshua Levitz,

Daniel J. Mandell,

Tanja Kortemme,

Jay T. Groves,

Howard Schulman,

John Kuriyan

Publication year - 2011

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2011.07.038

Subject(s) - biology , calmodulin , linker , protein kinase domain , kinase , microbiology and biotechnology , protein kinase a , biophysics , autophosphorylation , gene isoform , binding site , calcium , biochemistry , enzyme , chemistry , gene , mutant , organic chemistry , computer science , operating system

Calcium/calmodulin-dependent kinase II (CaMKII) forms a highly conserved dodecameric assembly that is sensitive to the frequency of calcium pulse trains. Neither the structure of the dodecameric assembly nor how it regulates CaMKII are known. We present the crystal structure of an autoinhibited full-length human CaMKII holoenzyme, revealing an unexpected compact arrangement of kinase domains docked against a central hub, with the calmodulin-binding sites completely inaccessible. We show that this compact docking is important for the autoinhibition of the kinase domains and for setting the calcium response of the holoenzyme. Comparison of CaMKII isoforms, which differ in the length of the linker between the kinase domain and the hub, demonstrates that these interactions can be strengthened or weakened by changes in linker length. This equilibrium between autoinhibited states provides a simple mechanism for tuning the calcium response without changes in either the hub or the kinase domains.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research