8arf | pdb_00008arf
Crystal structure of the N-terminal parallel dimeric coiled-coil region of the human kinetochore associated protein Spindly
Structural highlights
FunctionSPDLY_HUMAN Required for the localization of dynein and dynactin to the mitotic kintochore. Dynein is believed to control the initial lateral interaction between the kinetochore and spindle microtubules and to facilitate the subsequent formation of end-on kinetochore-microtubule attachments mediated by the NDC80 complex. Also required for correct spindle orientation. Does not appear to be required for the removal of spindle assembly checkpoint (SAC) proteins from the kinetochore upon bipolar spindle attachment (PubMed:17576797, PubMed:19468067). Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track) (PubMed:25035494). Plays a role in cell migration (PubMed:30258100).[HAMAP-Rule:MF_03041][1] [2] [3] [4] Publication Abstract from PubMedCytoplasmic Dynein 1, or Dynein, is a microtubule minus end-directed motor. Dynein motility requires Dynactin and a family of activating adaptors that stabilize the Dynein-Dynactin complex and promote regulated interactions with cargo in space and time. How activating adaptors limit Dynein activation to specialized subcellular locales is unclear. Here, we reveal that Spindly, a mitotic Dynein adaptor at the kinetochore corona, exists natively in a closed conformation that occludes binding of Dynein-Dynactin to its CC1 box and Spindly motif. A structure-based analysis identified various mutations promoting an open conformation of Spindly that binds Dynein-Dynactin. A region of Spindly downstream from the Spindly motif and not required for cargo binding faces the CC1 box and stabilizes the intramolecular closed conformation. This region is also required for robust kinetochore localization of Spindly, suggesting that kinetochores promote Spindly activation to recruit Dynein. Thus, our work illustrates how specific Dynein activation at a defined cellular locale may require multiple factors. Conformational transitions of the Spindly adaptor underlie its interaction with Dynein and Dynactin.,d'Amico EA, Ud Din Ahmad M, Cmentowski V, Girbig M, Muller F, Wohlgemuth S, Brockmeyer A, Maffini S, Janning P, Vetter IR, Carter AP, Perrakis A, Musacchio A J Cell Biol. 2022 Nov 7;221(11):e202206131. doi: 10.1083/jcb.202206131. Epub 2022 , Sep 15. PMID:36107127[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
