Abstract
The protein stromal interaction molecule 1 (STIM1) plays a pivotal role in mediating store-operated calcium entry (SOCE) into cells, which is essential for adaptive immunity. It acts as a calcium sensor in the endoplasmic reticulum (ER) and extends into the cytosol, where it changes from an inactive (tight) to an active (extended) oligomeric form upon calcium store depletion. NMR studies of this protein are challenging due to its membrane-spanning and aggregation properties. Therefore follow the divide-and-conquer approach, focusing on individual domains first is in order. The cytosolic part is predicted to have a large content of coiled-coil (CC) structure. We report the 1H, 13C, 15N chemical shift assignments of the CC3 domain. This domain is crucial for the stabilisation of the tight quiescent form of STIM1 as well as for activating the ORAI calcium channel by direct contact, in the extended active form.
Highlights
Calcium ions (Ca2+) play an essential role as second messengers in every cell. Ca2+ controls a variety of cellular processes including gene expression, cell division, neuronal signaling, muscle contraction, fertilization and apoptosis
The cytosolic portion of stromal interaction molecule 1 (STIM1) contains three coiled coil (CC) domains denoted as CC1, CC2, CC3 with CC1 subdivided into three alpha helices (α1, α2 and α3) (Rathner et al 2021)
We have reported complete backbone and near-complete side chain NMR resonance assignments of the human wildtype STIM1 CC3 domain
Summary
After a further oligomerization process potentially involving CC3, STIM1 couples to Orai and activates the channel (Muik et al 2009; Fahrner et al 2014, 2020; Rathner et al 2021; Zhou et al 2013). STIM1 CC3 is an essential domain with multiple functions: In resting cells, it stabilizes the protein in the quiescent tight state. Upon activation, it engages in STIM homo-oligomerization, supporting STIM1 cluster formation. The linker region between CC3 and CC2 is an important contact domain to Orai, essential for channel activation (Frischauf et al 2009; Muik et al 2009, 2011; Fahrner et al 2014; Zhou et al 2013).
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