Work

The Role of the S4-S5 Linker and C-terminal Tail in Inositol 1,4,5-Trisphosphate Receptor Function

Year: 2006

Type: article

Abstract: In previous studies we have suggested that spatial proximity of the C- and N-terminal domains of inositol 1,4,5-trisphosphate receptors (IP(3)Rs) may be critical for the channel gating mechanism. In the present study we have examined the sites of C-N interaction in more detail. We report that deletion mutations within the S4-S5 linker (amino acids 2418-2437) prevent co-immunoprecipitation of the C- and N-terminal domains, inhibit channel activity and enhance IP(3) binding. We also show that a region of the C-terminal tail (amino acids 2694-2721), predicted to be a coiled-coil, is also required for channel activity. Circular dichroism spectroscopy and gel filtration studies confirm that this region has a helical structure with the ability to form tetramers. We propose a model in which IP(3)-induced conformational changes in the N-terminal domain are mechanically transmitted to the opening of the pore through an attachment to the S4-S5 linker. The coiled-coil domain in the C-terminal tail may play a critical role in maintaining the structural integrity of the channel.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m604190200

Authors: Zachary T. Schug, Suresh K. Joseph

Institution: Thomas Jefferson University

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,430

Funders: National Institute on Alcohol Abuse and Alcoholism, National Institute of Diabetes and Digestive and Kidney Diseases