Skip to main content

A key to calcium signaling

Feb. 11, 2020, 8:00 AM

by Sanjay Mishra

IP3 receptors (IP3Rs) are calcium channels found in all animal cells. By mediating calcium ion release, IP3Rs integrate signals from different cellular pathways and metabolic states. Not surprisingly, deregulation of IP3Rs causes many diseases.

In mammals, there are three subtypes of IP3Rs, of which the type 3 receptor is found predominantly in rapidly proliferating cells including several cancers. However, due to their large size and subunit diversity, the structure of IP3Rs has not yet been fully characterized.

Now, in a study published in the Journal of Biological Chemistry, Erkan Karakas, PhD, and colleagues present a structure of the human IP3R type 3 in its ligand-free state.

Their structure, discovered through cryo-electron microscopy, identified previously unresolved local structures, the location of lipid biding sites and the presence of a self-binding peptide (SBP) that occupies the IP3 binding site and competitively inhibits IP3 binding.

The researchers concluded that the SBP could be a key molecular determinant of subtype-specific calcium signaling in IP3Rs.

This research was supported by the National Institutes of Health (grants DK020593, HD061543, GM008320) and by Vanderbilt University.

Recent Stories from VUMC News and Communications Publications

Betsy Williams has firsthand advice for parents on the fence about whether their adolescent children should be vaccinated for the common human papilloma virus (HPV), which can lead to six types of cancer.  Don’t hesitate. Do it.

Momentum

Betsy Williams has firsthand advice for parents on the fence about whether their adolescent children should be vaccinated for the common human papilloma virus (HPV), which can lead to six types of cancer. Don’t hesitate. Do it.

Keeping pace: Nashville, once a mid-size city with a Southern small-town feel, is experiencing explosive growth.

Vanderbilt Medicine

Keeping pace: Nashville, once a mid-size city with a Southern small-town feel, is experiencing explosive growth.

VUMC campus

VUMC campus

Vanderbilt University School of Medicine entrance

Vanderbilt University School of Medicine entrance

more