Binding of the erlin1/2 complex to the third intralumenal loop of IP₃R1 triggers its ubiquitin-proteasomal degradation.

ABSTRACT: Long-term activation of inositol 1,4,5-trisphosphate receptors (IP₃Rs) leads to their degradation by the ubiquitin-proteasome pathway. The first and rate-limiting step in this process is thought to be the association of conformationally active IP₃Rs with the erlin1/2 complex, an endoplasmic reticulum-located oligomer of erlin1 and erlin2 that recruits the E3 ubiquitin ligase RNF170, but the molecular determinants of this interaction remain unknown. Here, through mutation of IP₃R1, we show that the erlin1/2 complex interacts with the IP₃R1 intralumenal loop 3 (IL3), the loop between transmembrane (TM) helices 5 and 6, and in particular, with a region close to TM5, since mutation of amino acids D-2471 and R-2472 can specifically block erlin1/2 comp

SUBMITTER: Gao X 

PROVIDER: S-EPMC9168715 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature