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Molecular basis of mRNA transport by a kinesin-1–atypical tropomyosin complex
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 oocy...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247599/ https://www.ncbi.nlm.nih.gov/pubmed/34140355 http://dx.doi.org/10.1101/gad.348443.121 |
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author | Dimitrova-Paternoga, Lyudmila Jagtap, Pravin Kumar Ankush Cyrklaff, Anna Vaishali, Lapouge, Karine Sehr, Peter Perez, Kathryn Heber, Simone Löw, Christian Hennig, Janosch Ephrussi, Anne |
author_facet | Dimitrova-Paternoga, Lyudmila Jagtap, Pravin Kumar Ankush Cyrklaff, Anna Vaishali, Lapouge, Karine Sehr, Peter Perez, Kathryn Heber, Simone Löw, Christian Hennig, Janosch Ephrussi, Anne |
author_sort | Dimitrova-Paternoga, Lyudmila |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8247599 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-82475992021-07-20 Molecular basis of mRNA transport by a kinesin-1–atypical tropomyosin complex Dimitrova-Paternoga, Lyudmila Jagtap, Pravin Kumar Ankush Cyrklaff, Anna Vaishali, Lapouge, Karine Sehr, Peter Perez, Kathryn Heber, Simone Löw, Christian Hennig, Janosch Ephrussi, Anne Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2021-07-01 /pmc/articles/PMC8247599/ /pubmed/34140355 http://dx.doi.org/10.1101/gad.348443.121 Text en © 2021 Dimitrova-Paternoga et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by-nc/4.0/This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Research Paper 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 |
title | Molecular basis of mRNA transport by a kinesin-1–atypical tropomyosin complex |
title_full | Molecular basis of mRNA transport by a kinesin-1–atypical tropomyosin complex |
title_fullStr | Molecular basis of mRNA transport by a kinesin-1–atypical tropomyosin complex |
title_full_unstemmed | Molecular basis of mRNA transport by a kinesin-1–atypical tropomyosin complex |
title_short | Molecular basis of mRNA transport by a kinesin-1–atypical tropomyosin complex |
title_sort | molecular basis of mrna transport by a kinesin-1–atypical tropomyosin complex |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247599/ https://www.ncbi.nlm.nih.gov/pubmed/34140355 http://dx.doi.org/10.1101/gad.348443.121 |
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