Molecular basis of mRNA transport by a kinesin-1-atypical tropomyosin complex

• Verfasst von: Dimitrova-Paternoga, Lyudmila Nikolova [VerfasserIn]
• Verfasst von: Jagtap, Pravin Kumar Ankush [VerfasserIn]
• Verfasst von: Cyrklaff, Anna [VerfasserIn]
• Verfasst von: Vaishali [VerfasserIn]
• Verfasst von: Lapouge, Karine [VerfasserIn]
• Verfasst von: Sehr, Peter [VerfasserIn]
• Verfasst von: Perez, Kathryn [VerfasserIn]
• Verfasst von: Heber, Simone [VerfasserIn]
• Verfasst von: Löw, Christian [VerfasserIn]
• Verfasst von: Hennig, Janosch [VerfasserIn]
• Verfasst von: Ephrussi, Anne [VerfasserIn]
• Titel: Molecular basis of mRNA transport by a kinesin-1-atypical tropomyosin complex
• Verf.angabe: Lyudmila Dimitrova-Paternoga, Pravin Kumar Ankush Jagtap, Anna Cyrklaff, Vaishali, Karine Lapouge, Peter Sehr, Kathryn Perez, Simone Heber, Christian Löw, Janosch Hennig, and Anne Ephrussi
• Jahr: 2021
• Umfang: 16 S.
• Fussnoten: Gesehen am 26.09.2021
• Titel Quelle: Enthalten in: Genes & development
• Ort Quelle: Stanford, Calif. : HighWire Press, 1987
• Jahr Quelle: 2021
• Band/Heft Quelle: 35(2021), 13/14, Seite 976-991
• ISSN Quelle: 1549-5477
• DOI: doi:10.1101/gad.348443.121
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: kinesin
• Sach-SW: kinesin adaptor
• Sach-SW: kinesin-atypical tropomyosin complex
• Sach-SW: mRNA transport
• Sach-SW: oskar mRNA
• K10plus-PPN: 1771804769

Abstract

Kinesin-1 carries cargos including proteins, RNAs, vesicles, and pathogens over long distances within cells. The mechanochemical cycle of kinesins is well described, but how they establish cargo specificity is not fully understood. Transport of oskar mRNA to the posterior pole of the Drosophila oocyte is mediated by Drosophila kinesin-1, also called kinesin heavy chain (Khc), and a putative cargo adaptor, the atypical tropomyosin, aTm1. How the proteins cooperate in mRNA transport is unknown. Here, we present the high-resolution crystal structure of a Khc-aTm1 complex. The proteins form a tripartite coiled coil comprising two in-register Khc chains and one aTm1 chain, in antiparallel orientation. We show that aTm1 binds to an evolutionarily conserved cargo binding site on Khc, and mutational analysis confirms the importance of this interaction for mRNA transport in vivo. Furthermore, we demonstrate that Khc binds RNA directly and that it does so via its alternative cargo binding domain, which forms a positively charged joint surface with aTm1, as well as through its adjacent auxiliary microtubule binding domain. Finally, we show that aTm1 plays a stabilizing role in the interaction of Khc with RNA, which distinguishes aTm1 from classical motor adaptors.