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Conformational plasticity of the ULK3 kinase domain

DOI: 10.1042/BCJ20210257 DOI Help

Authors: Sebastian Mathea (Goethe-University Frankfurt) , Eidarus Salah (University of Oxford) , Cynthia Tallant (Structural Genomics Consortium, University of Oxford) , Deep Chatterjee (Goethe-University Frankfurt) , Benedict-Tilman Berger (Goethe-University Frankfurt) , Rebecca Konietzny (University of Oxford) , Susanne Müller-Knapp (Goethe-University Frankfurt) , Benedikt M Kessler (University of Oxford) , Stefan Knapp (Goethe-University Frankfurt)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochemical Journal

State: Published (Approved)
Published: June 2021

Open Access Open Access

Abstract: The human protein kinase ULK3 regulates the timing of membrane abscission, thus being involved in exosome budding and cytokinesis. Herein, we present the first high-resolution structures of the ULK3 kinase domain. Its unique features are explored against the background of other ULK kinases. An inhibitor fingerprint indicates that ULK3 is highly druggable and capable of adopting a wide range of conformations. In accordance with this, we describe a conformational switch between the active and an inactive ULK3 conformation, controlled by the properties of the attached small-molecule binder. Finally, we discuss a potential substrate-recognition mechanism of the full-length ULK3 protein.

Journal Keywords: ULK kinase; enzyme-substrate interactions; phosphorylation; conformational changes; small-molecule inhibitor

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 05/07/2021 11:54


Discipline Tags:

Health & Wellbeing Biochemistry Chemistry Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)