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

Title data

Dimitrova-Paternoga, Lyudmila ; Jagtap, Pravin Kumar Ankush ; Cyrklaff, Anna ; Vaishali, ; Lapouge, Karine ; Sehr, Peter ; Perez, Kathryn ; Heber, Simone ; Löw, Christian ; Hennig, Janosch ; Ephrussi, Anne:
Molecular basis of mRNA transport by a kinesin-1-atypical tropomyosin complex.
In: Genes & Development. Vol. 35 (2021) Issue 13-14 . - pp. 976-991.
ISSN 1549-5477
DOI: https://doi.org/10.1101/gad.348443.121

Project information

Project financing: Deutsche Forschungsgemeinschaft

Abstract in another language

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.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: kinesin; kinesin adaptor; kinesin–atypical tropomyosin complex; mRNA transport; oskar mRNA
Institutions of the University: Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry with an Emphasis on Biophysical Chemistry > Chair Biochemistry with an Emphasis on Biophysical Chemistry - Univ.-Prof. Dr. Janosch Hennig
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry with an Emphasis on Biophysical Chemistry
Result of work at the UBT: No
DDC Subjects: 500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 09 Sep 2021 08:54
Last Modified: 22 Oct 2021 10:34
URI: https://eref.uni-bayreuth.de/id/eprint/66991