Academic Journal
How the non-motile kinesin KIF7 adapts conserved kinesin principles for its function in Hedgehog signaling.
| Τίτλος: | How the non-motile kinesin KIF7 adapts conserved kinesin principles for its function in Hedgehog signaling. |
|---|---|
| Συγγραφείς: | Haque F; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Srinivasu BY; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA., Engen JR; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA., Wales TE; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA., Subramanian R; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. |
| Πηγή: | BioRxiv : the preprint server for biology [bioRxiv] 2026 Feb 10. Date of Electronic Publication: 2026 Feb 10. |
| Τύπος έκδοσης: | Journal Article; Preprint |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| Περίληψη: | KIF7 is an atypical, non-motile kinesin that regulates Hedgehog signaling by concentrating GLI transcription factors at the cilium tip. How canonical kinesin principles for intracellular transport are repurposed to support KIF7's function as a signaling scaffold remains unclear. KIF7 exists in an autoinhibited state that is relieved by GLI binding, promoting microtubule association. We examined this regulatory mechanism by combining HDX-MS and AlphaFold modeling of a minimal KIF7 dimer, both alone and in complex with the GLI2 zinc-finger domain. Our HDX-MS data indicate that the highly negatively charged neck-coil dimerization domain of KIF7, which serves as the GLI2-binding site, is intramolecularly protected in the absence of GLI2. Consistent with this, AlphaFold models suggest that the motor domain folds back onto the neck-coil via KIF7's unusually long neck-linker, sterically occluding the microtubule-binding interface. This occurs through a mechanism conceptually analogous to, but structurally distinct from, autoinhibition in motile kinesins. GLI2 binding to the KIF7 neck-coil displaces the motor domain and induces allosteric changes that propagate to the microtubule-binding surface, thereby activating microtubule binding. ATP turnover further modulates KIF7's microtubule binding-unbinding equilibrium. Together, these findings reveal how a kinesin is adapted for a non-motile function as a scaffold in Hedgehog signaling. |
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| Grant Information: | R01 GM145651 United States GM NIGMS NIH HHS |
| Entry Date(s): | Date Created: 20260223 Date Completed: 20261020 Latest Revision: 20261020 |
| Update Code: | 20261020 |
| PubMed Central ID: | PMC12919046 |
| DOI: | 10.64898/2026.02.06.704517 |
| PMID: | 41727108 |
| Βάση Δεδομένων: | MEDLINE |
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