Details

Autor(en) / Beteiligte

• Dimitrova-Paternoga, Lyudmila
• Jagtap, Pravin Kumar Ankush
• Cyrklaff, Anna
• Vaishali
• Lapouge, Karine
• Sehr, Peter
• Perez, Kathryn
• Heber, Simone
• Löw, Christian
• Hennig, Janosch
• Ephrussi, Anne

Titel

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

Ist Teil von

• Genes & development, 2021-07, Vol.35 (13-14), p.976-991

Ort / Verlag

United States: Cold Spring Harbor Laboratory Press

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 mRNA to the posterior pole of the oocyte is mediated by kinesin-1, also called kinesin heavy chain (Khc), and a putative cargo adaptor, the atypical tropomyosin, Tm1. How the proteins cooperate in mRNA transport is unknown. Here, we present the high-resolution crystal structure of a Khc- Tm1 complex. The proteins form a tripartite coiled coil comprising two in-register Khc chains and one Tm1 chain, in antiparallel orientation. We show that Tm1 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 Tm1, as well as through its adjacent auxiliary microtubule binding domain. Finally, we show that Tm1 plays a stabilizing role in the interaction of Khc with RNA, which distinguishes Tm1 from classical motor adaptors.