The two‐step cargo recognition mechanism of heterotrimeric kinesin-Reference-Cited by-同舟云学术

The two‐step cargo recognition mechanism of heterotrimeric kinesin

Published:2023-08-14 Issue:11 Volume:24 Page:
ISSN:1469-221X
Container-title:EMBO reports
language:en
Short-container-title:EMBO Reports

Author:

Jiang Xuguang¹²^ORCID,Ogawa Tadayuki¹³⁴^ORCID,Yonezawa Kento⁵⁶^ORCID,Shimizu Nobutaka⁵^ORCID,Ichinose Sotaro¹⁷^ORCID,Uchihashi Takayuki⁸⁹^ORCID,Nagaike Wataru⁸,Moriya Toshio⁵^ORCID,Adachi Naruhiko⁵^ORCID,Kawasaki Masato⁵,Dohmae Naoshi⁴^ORCID,Senda Toshiya⁵^ORCID,Hirokawa Nobutaka¹¹⁰^ORCID

Affiliation:

1. Department of Cell Biology and Anatomy, Graduate School of Medicine The University of Tokyo Tokyo Japan

2. Tsinghua‐Peking Center for Life Sciences, School of Life Sciences Tsinghua University Beijing China

3. Research Center for Advanced Medical Science Dokkyo Medical University Tochigi Japan

4. Biomolecular Characterization Unit RIKEN Center for Sustainable Resource Science Wako Japan

5. Structural Biology Research Center, Photon Factory Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK) Tsukuba Japan

6. Center for Digital Green‐Innovation Nara Institute of Science and Technology Nara Japan

7. Department of Anatomy, Graduate School of Medicine Gunma University Gunma Japan

8. Department of Physics Nagoya University Nagoya Japan

9. Exploratory Research Center on Life and Living Systems (ExCELLS) National Institutes of Natural Sciences Okazaki Japan

10. Juntendo Advanced Research Institute for Health Science Juntendo University Tokyo Japan

Abstract

AbstractKinesin‐driven intracellular transport is essential for various cell biological events and thus plays a crucial role in many pathological processes. However, little is known about the molecular basis of the specific and dynamic cargo‐binding mechanism of kinesins. Here, an integrated structural analysis of the KIF3/KAP3 and KIF3/KAP3‐APC complexes unveils the mechanism by which KIF3/KAP3 can dynamically grasp APC in a two‐step manner, which suggests kinesin‐cargo recognition dynamics composed of cargo loading, locking, and release. Our finding is the first demonstration of the two‐step cargo recognition and stabilization mechanism of kinesins, which provides novel insights into the intracellular trafficking machinery.

Funder

Japan Agency for Medical Research and Development

Japan Society for the Promotion of Science

Publisher

Springer Science and Business Media LLC

Subject

Genetics,Molecular Biology,Biochemistry

Link

https://www.embopress.org/doi/pdf/10.15252/embr.202356864

Reference67 articles.

1. Kinesin family in murine central nervous system.

2. Kinesin Kif3b mutation reduces NMDAR subunit NR 2A trafficking and causes schizophrenia‐like phenotypes in mice

3. High-speed atomic force microscopy

4. A high-speed atomic force microscope for studying biological macromolecules

5. A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs