Daria Trofimova, Caitlin Doubleday, Byron Hunter, Jesus Danilo Serrano Arevalo, Emma Davison, Eric Wen, Kim Munro, John S. Allingham
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Fungal kinesin-8 motors dimerize by folding their proximal tail domain into a compact helical bundle
Kinesin-8 motors regulate kinetochore-microtubule dynamics and control spindle length and positioning. Certain isoforms achieve this by traversing microtubules, accumulating at plus-ends, and depolymerizing terminal αβ-tubulin subunits. While the kinesin-8 motor domain is well characterized, the tail domain regions are less understood. Using the Candida albicans Kip3 protein as a model for fungal kinesin-8, we present an X-ray crystal structure and hydrodynamic analysis of its motor-proximal tail segment, revealing its role in motor dimerization. This segment forms a compact, 92 Å-long four-helix bundle, rather than an elongated coiled-coil stalk seen in most kinesins. The bundle is stabilized primarily by interactions between helices one and three, with additional support from helices two and four. A flexible hinge bisects the bundle into two lobules, imparting mechanical pliability and asymmetric exterior surfaces. These unique features may facilitate interactions with regulatory elements or contribute to the functional versatility of kinesin-8 motors.
期刊介绍:
Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome.
In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.