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Structural characterization of inositol 1,4,5-triphosphate receptors


EMSL Project ID
51589

Abstract

Inositol 1,4,5-triphosphate receptors (IP3Rs) function as signaling hubs integrating diverse signals to regulate many physiological processes. Pathological dysregulation of IP3Rs and calcium signaling is implicated in cancer, neurodegenerative, autoimmune, and metabolic diseases. IP3Rs are ligand-gated Ca2+-release channels localized predominantly in the endoplasmic reticulum (ER) membrane of all cell types. Recent structural studies revealed IP3R architecture, but fundamental questions regarding the mechanisms of ligand interactions and channel gating remain mostly unanswered. We recently collected a dataset at the PNCC, and solved the structure of human type-3 IP3R (hIP3R-3) in an open, activated conformation at an overall resolution of 6.1 Å. In this proposal, we aim to collect a high quality dataset to improve the resolution beyond 4Å. The new structure of hIP3R-3 will be the first structure of IP3Rs in an open, activated conformation, and will reveal fundamental insight into gating mechanism of IP3Rs.

Project Details

Start Date
2020-08-15
End Date
2020-11-15
Status
Closed

Team

Principal Investigator

Erkan Karakas
Institution
Vanderbilt University