SOAR and the polybasic STIM1 domains gate and regulate the Orai channels

By Joseph P. Yuan, W. Zeng, M. Dorwart, Y. Choi, P. Worley, S. Muallem. Nature Cell Biology, 2009

685 citations recorded by the source corpus.

Influx of Ca2+ through store-operated Ca2+ channels (SOCs) is a central component of receptor-evoked Ca2+ signals. Orai channels are SOCs that are gated by STIM1, a Ca2+ sensor located in the ER but how it gates and regulates the Orai channels is unknown. Here, we report the molecular basis for gating of Orais by STIM1. All Orai channels are fully activated by the conserved STIM1 amino acid fragment 344–442, which we termed SOAR (the STIM1 Orai activating region). SOAR acts in combination with STIM1 (450–485) to regulate the strength of interaction with Orai1. Activation of Orai1 by SOAR recapitulates all the kinetic properties of Orai1 activation by STIM1. However, mutations of STIM1 within SOAR prevent activation of Orai1 but not co-clustering of STIM1 and Orai1 in response to Ca2+ store depletion, indicating that STIM1–Orai1 co-clustering is not sufficient for Orai1 activation. An intact carboxy terminus α-helicial region of Orai is required for activation by SOAR. Deleting most of the Orai1 amino terminus impaired Orai1 activation by STIM1, but Orai1Δ1–73 interacted with and was fully activated by SOAR. Accordingly, the characteristic inward rectification of Orai is mediated by an interaction between the polybasic STIM1 (672–685) and a Pro-rich region in the N terminus of Orai1. Hence, the essential properties of Orai1 function can be rationalized by interactions with discrete regions of STIM1.

Subfields: Biochemistry, Cellular and Molecular Neuroscience, Sensory Systems

View Paper: https://www.semanticscholar.org/paper/3c9eb414db00bc7f6f1d10d4a82448b74dcd8482

How researchers see this paper

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In Cellular and Molecular Neuroscience

1. R. Lewis
2. Jie Zheng
3. M. Trudeau

In Sensory Systems

1. R. Lewis
2. Jie Zheng
3. M. Trudeau
4. Anjana Rao
5. P. Hogan
6. M. Cahalan
7. M. Prakriya
8. S. Feske

Citations in the corpus

• Handbook of ion channels (2015, background): “This region is variously called the CRAC activation domain (CAD) [40], STIM1–ORAI1 activating region (SOAR) [42], or Ccb9 [101] and includes the amino acids 342–444.”
• The functional network of ion channels in T lymphocytes (2009, background): “Expression of the C-terminus as a cytosolic protein effectively activates CRAC current through the Orai1 (or Orai) channel (94, 99–103), as do fragments of the C-terminus as small as 100 amino acids corresponding to the distal coiled-coil domain (96, 104, 105).”
• Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI (2010, background): “The minimal region, termed SOAR (STIM-ORAI activating region), CAD, or CCb9, encompasses roughly residues 344–442 (32, 33, 35) and is contained within the functionally similar fragment termed OASF (ORAI1 activating STIM1 small C-terminal fragment) (34) (Figure 2).”