7BJS

Crystal structure of Khc/atypical Tm1 complex

Summary for 7BJS

• Entry DOI: 10.2210/pdb7bjs/pdb
• Descriptor: Kinesin heavy chain, SD21996p (3 entities in total)
• Functional Keywords: triple coiled-coil, mrna transport, protein-protein complex, drosophila oocyte, transport protein
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 3
• Total formula weight: 30928.59

Authors

Dimitrova-Paternoga, L.,Jagtap, P.K.A.,Ephrussi, A.,Hennig, J. (deposition date: 2021-01-14, release date: 2021-05-26, Last modification date: 2024-05-01)

Primary citation

Dimitrova-Paternoga, L.,Jagtap, P.K.A.,Cyrklaff, A.,Lapouge, K.,Sehr, P.,Perez, K.,Heber, S.,Low, C.,Hennig, J.,Ephrussi, A.
Molecular basis of mRNA transport by a kinesin-1-atypical tropomyosin complex.
Genes Dev., 35:976-991, 2021

PubMed 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 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.

PubMed: 34140355
DOI: 10.1101/gad.348443.121

Experimental method

X-RAY DIFFRACTION (2.28 Å)