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TitleConformational alteration of DOCK5•ELMO1 signalosome on lipid membrane.
Journal, issue, pagesCommun Biol, Vol. 8, Issue 1, Page 1523, Year 2025
Publish dateNov 13, 2025
AuthorsTakehiro Shinoda / Kazushige Katsura / Yoshiko Ishizuka-Katsura / Kazuharu Hanada / Mayumi Yonemochi / Yuki Miyamoto / Mutsuko Kukimoto-Niino / Junji Yamauchi / Mikako Shirouzu /
PubMed AbstractThe DOCK protein family activates Rho small GTPases through guanine nucleotide exchange factor (GEF) activity. DOCK is thought to exert its GEF activity at the plasma membrane. However, the mechanism ...The DOCK protein family activates Rho small GTPases through guanine nucleotide exchange factor (GEF) activity. DOCK is thought to exert its GEF activity at the plasma membrane. However, the mechanism by which DOCK activity on the plasma membrane is regulated remains unclear. Herein, we present a new conformation in which DOCK5, ELMO1, RhoG, and Rac1 are aligned on a plane and symmetrically flattened, as revealed by cryo-EM using a lipid membrane-coated grid. The major conformational change leading to this structure results from rotation of each DOCK5•ELMO1 hinge site through interactions with the membrane. Biochemical and cellular experiments indicate that conformational changes driven by acidic lipids are important for regulating the GEF activity of the DOCK5•ELMO1 complex on the plasma membrane and are essential for its downstream signalling. This approach also enables the analysis of large lipid-associated complexes, such as signalosomes, and will aid studies of membrane-dependent signalling assemblies.
External linksCommun Biol / PubMed:41233496 / PubMed Central
MethodsEM (single particle)
Resolution6.98 - 7.52 Å
Structure data

63464

9lx0

EMDB-63464, PDB-9lx0:
DOCK5/ELMO1 complex with RhoG and Rac1 on lipid membrane
Method: EM (single particle) / Resolution: 6.98 Å

63477

9lxh

EMDB-63477, PDB-9lxh:
DOCK5/ELMO1 complex with RhoG and Rac1 on lipid membrane
Method: EM (single particle) / Resolution: 7.52 Å

Source
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / Complex / Rho-GTPase / GEF / Lipid membrane

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