Calcium sensing by the STIM1 ER-luminal domain. Academic Article uri icon


  • Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca2+ levels to maintain cellular Ca2+ balance and to support Ca2+ signalling. The prevailing view has been that STIM1 senses reduced ER Ca2+ through dissociation of bound Ca2+ from a single EF-hand site, which triggers a dramatic loss of secondary structure and dimerization of the STIM1 luminal domain. Here we find that the STIM1 luminal domain has 5-6 Ca2+-binding sites, that binding at these sites is energetically coupled to binding at the EF-hand site, and that Ca2+ dissociation controls a switch to a second structured conformation of the luminal domain rather than protein unfolding. Importantly, the other luminal-domain Ca2+-binding sites interact with the EF-hand site to control physiological activation of STIM1 in cells. These findings fundamentally revise our understanding of physiological Ca2+ sensing by STIM1, and highlight molecular mechanisms that govern the Ca2+ threshold for activation and the steep Ca2+ concentration dependence.

published proceedings

  • Nat Commun

altmetric score

  • 51.85

author list (cited authors)

  • Gudlur, A., Zeraik, A. E., Hirve, N., Rajanikanth, V., Bobkov, A. A., Ma, G., ... Hogan, P. G.

citation count

  • 41

complete list of authors

  • Gudlur, Aparna||Zeraik, Ana Eliza||Hirve, Nupura||Rajanikanth, V||Bobkov, Andrey A||Ma, Guolin||Zheng, Sisi||Wang, Youjun||Zhou, Yubin||Komives, Elizabeth A||Hogan, Patrick G

publication date

  • January 2018