7E1T

Crystal structure of Rab9A-GTP-Nde1

Summary for 7E1T

• Entry DOI: 10.2210/pdb7e1t/pdb
• Descriptor: Ras-related protein Rab-9A, Isoform 2 of Nuclear distribution protein nudE homolog 1, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: rab9a, nde1, rab gtpase, effector, protein transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 64151.41

Authors

Zhang, Y.,Zhang, T.,Ding, J. (deposition date: 2021-02-03, release date: 2021-10-27, Last modification date: 2023-11-29)

Primary citation

Zhang, Y.,Chen, Z.,Wang, F.,Sun, H.,Zhu, X.,Ding, J.,Zhang, T.
Nde1 is a Rab9 effector for loading late endosomes to cytoplasmic dynein motor complex.
Structure, 30:386-395.e5, 2022

PubMed Abstract: Rab9 is mainly located on late endosomes and required for their intracellular transport to trans-Golgi network (TGN). The cytoplasmic dynein motor, together with its regulatory proteins Nde1/Ndel1 and Lis1, controls intracellular retrograde transport of membranous organelles along the microtubule network. How late endosomes are tethered to the microtubule-based motor dynein for their retrograde transport remains unclear. Here, we demonstrate that the guanosine triphosphate (GTP)-bound Rab9A/B specifically uses Nde1/Ndel1 as an effector to interact with the dynein motor complex. We determined the crystal structure of Rab9A-GTP in complex with the Rab9-binding region of Nde1. The functional roles of key residues involved in the Rab9A-Nde1 interaction are verified using biochemical and cell biology assays. Rab9A mutants unable to bind to Nde1 also failed to associate with dynein, Lis1, and dynactin. Therefore, Nde1 is a Rab9 effector that tethers Rab9-associated late endosomes to the dynein motor for their retrograde transport to the TGN.

PubMed: 34793709
DOI: 10.1016/j.str.2021.10.013

Experimental method

X-RAY DIFFRACTION (2.45 Å)