7DPA

Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex

Summary for 7DPA

• Entry DOI: 10.2210/pdb7dpa/pdb
• EMDB information: 30802
• Descriptor: Dedicator of cytokinesis protein 5, Ras-related C3 botulinum toxin substrate 1, Engulfment and cell motility protein 1 (3 entities in total)
• Functional Keywords: elmo, dock, gef, gtpase, rho, rac, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 592148.20

Authors

Kukimoto-Niino, M.,Katsura, K.,Kaushik, R.,Ehara, H.,Yokoyama, T.,Uchikubo-Kamo, T.,Mishima-Tsumagari, C.,Yonemochi, M.,Ikeda, M.,Hanada, K.,Zhang, K.Y.J.,Shirouzu, M. (deposition date: 2020-12-18, release date: 2021-08-04, Last modification date: 2024-03-27)

Primary citation

Kukimoto-Niino, M.,Katsura, K.,Kaushik, R.,Ehara, H.,Yokoyama, T.,Uchikubo-Kamo, T.,Nakagawa, R.,Mishima-Tsumagari, C.,Yonemochi, M.,Ikeda, M.,Hanada, K.,Zhang, K.Y.J.,Shirouzu, M.
Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex.
Sci Adv, 7:-, 2021

PubMed Abstract: The dedicator of cytokinesis (DOCK) family of guanine nucleotide exchange factors (GEFs) promotes cell motility, phagocytosis, and cancer metastasis through activation of Rho guanosine triphosphatases. Engulfment and cell motility (ELMO) proteins are binding partners of DOCK and regulate Rac activation. Here, we report the cryo-electron microscopy structure of the active ELMO1-DOCK5 complex bound to Rac1 at 3.8-Å resolution. The C-terminal region of ELMO1, including the pleckstrin homology (PH) domain, aids in the binding of the catalytic DOCK homology region 2 (DHR-2) domain of DOCK5 to Rac1 in its nucleotide-free state. A complex α-helical scaffold between ELMO1 and DOCK5 stabilizes the binding of Rac1. Mutagenesis studies revealed that the PH domain of ELMO1 enhances the GEF activity of DOCK5 through specific interactions with Rac1. The structure provides insights into how ELMO modulates the biochemical activity of DOCK and how Rac selectivity is achieved by ELMO.

PubMed: 34290093
DOI: 10.1126/sciadv.abg3147

Experimental method

ELECTRON MICROSCOPY (3.8 Å)