9KNS

Crystal structure of Hook3(553-624)

Summary for 9KNS

• Entry DOI: 10.2210/pdb9kns/pdb
• Descriptor: Protein Hook homolog 3 (2 entities in total)
• Functional Keywords: hook3, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 18484.21

Authors

Ku, B.,Lee, H.S. (deposition date: 2024-11-19, release date: 2025-02-26, Last modification date: 2025-05-14)

Primary citation

Lee, H.S.,Yu, D.,Baek, K.E.,Shin, H.C.,Kim, S.J.,Do Heo, W.,Ku, B.
Molecular basis for assembly and activation of the Hook3 - KIF1C complex-dependent transport machinery.
Embo Rep., 2025

PubMed Abstract: Microtubule-associated cargo transport, a central process governing the localization and movement of various cellular cargoes, is orchestrated by the coordination of two types of motor proteins (kinesins and dyneins), along with diverse adaptor and accessory proteins. Hook microtubule tethering protein 3 (Hook3) is a cargo adaptor that serves as a scaffold for recruiting kinesin family member 1C (KIF1C) and dynein, thereby regulating bidirectional cargo transport. Herein, we conduct structural and functional analyses of how Hook3 mediates KIF1C-dependent anterograde cargo transport through interaction with KIF1C and PTPN21. We verify the interactions among the three proteins and determine the crystal structure of the Hook3(553-624) - KIF1C(714-809) complex. Subsequent structure-based mutational analysis demonstrates that this complex formation is necessary and sufficient for the interaction between the full-length proteins in HEK293T cells and plays a key role in Hook3- and KIF1C-mediated anterograde transport in RPE1 cells. Thus, this study provides a basis for a comprehensive understanding of how Hook3 cooperates with other components during the initial steps of activation and assembly of the Hook3- and KIF1C-dependent cargo transport machinery.

PubMed: 40312563
DOI: 10.1038/s44319-025-00458-w

Experimental method

X-RAY DIFFRACTION (2.699 Å)