Duc Minh Nguyen, Deanna H Rath, Dominic Devost, Darlaine Pétrin, Robert Rizk, Alan X Ji, Naveen Narayanan, Darren Yong, Andrew Zhai, Douglas A Kuntz, Maha U Q Mian, Neil C Pomroy, Alexander F A Keszei, Samir Benlekbir, Mohammad T Mazhab-Jafari, John L Rubinstein, Terence E Hébert, Gilbert G Privé
Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain, engages CUL3 to form the central scaffold of a cullin-RING E3 ligase complex (CRL3KCTD5 ) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3NTD /Gβ1 γ2 assembly reveals a highly dynamic complex with rotations of over 60° between the KCTD5BTB /CUL3NTD and KCTD5CTD /Gβγ moieties of the structure...
April 23, 2024: Proceedings of the National Academy of Sciences of the United States of America