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An aromatic amino acid in the coiled-coil 1 domain plays a crucial role in the auto-inhibitory mechanism of STIM1.
Biochem J. 2013 Sep 15; 454(3):401-9.BJ

Abstract

STIM1 (stromal interaction molecule 1) is one of the key elements that mediate store-operated Ca²⁺ entry via CRAC (Ca²⁺- release-activated Ca²⁺) channels in immune and non-excitable cells. Under physiological conditions, the intramolecular auto-inhibitions in STIM1 C- and STIM1 N-termini play essential roles in keeping STIM1 in an inactive state. However, the auto-inhibitory mechanism of the STIM1 C-terminus is still unclear. In the present study, we first predicted a short inhibitory domain (residues 310-317) in human STIM1 that might determine the different localizations of human STIM1 from Caenorhabditis elegans STIM1 in resting cells. Next, we confirmed the prediction and further identified an aromatic amino acid residue, Tyr³¹⁶, that played a crucial role in maintaining STIM1 in a closed conformation in quiescent cells. Full-length STIM1-Y316A formed constitutive clusters near the plasma membrane and activated the CRAC channel in the resting state when co-expressed with Orai1. The introduction of a Y316A mutation caused the higher-order oligomerization of the in vitro purified STIM1 fragment containing both the auto-inhibitory domain and CAD(CRAC-activating domain).We propose that the Tyr³¹⁶ residue may be involved in the auto-inhibitory mechanism of the STIM1 C-terminus in the quiescent state. This inhibition could be achieved either by interacting with the CAD using hydrogen and/or hydrophobic bonds, or by an intermolecular interaction using repulsive forces, which maintained a dimeric STIM1.

Authors+Show Affiliations

College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23795811

Citation

Yu, Junwei, et al. "An Aromatic Amino Acid in the Coiled-coil 1 Domain Plays a Crucial Role in the Auto-inhibitory Mechanism of STIM1." The Biochemical Journal, vol. 454, no. 3, 2013, pp. 401-9.
Yu J, Zhang H, Zhang M, et al. An aromatic amino acid in the coiled-coil 1 domain plays a crucial role in the auto-inhibitory mechanism of STIM1. Biochem J. 2013;454(3):401-9.
Yu, J., Zhang, H., Zhang, M., Deng, Y., Wang, H., Lu, J., Xu, T., & Xu, P. (2013). An aromatic amino acid in the coiled-coil 1 domain plays a crucial role in the auto-inhibitory mechanism of STIM1. The Biochemical Journal, 454(3), 401-9.
Yu J, et al. An Aromatic Amino Acid in the Coiled-coil 1 Domain Plays a Crucial Role in the Auto-inhibitory Mechanism of STIM1. Biochem J. 2013 Sep 15;454(3):401-9. PubMed PMID: 23795811.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An aromatic amino acid in the coiled-coil 1 domain plays a crucial role in the auto-inhibitory mechanism of STIM1. AU - Yu,Junwei, AU - Zhang,Haining, AU - Zhang,Mingshu, AU - Deng,Yongqiang, AU - Wang,Huiyu, AU - Lu,Jingze, AU - Xu,Tao, AU - Xu,Pingyong, PY - 2013/02/25/received PY - 2013/06/21/revised PY - 2013/06/25/accepted PY - 2013/6/26/entrez PY - 2013/6/26/pubmed PY - 2013/11/5/medline SP - 401 EP - 9 JF - The Biochemical journal JO - Biochem J VL - 454 IS - 3 N2 - STIM1 (stromal interaction molecule 1) is one of the key elements that mediate store-operated Ca²⁺ entry via CRAC (Ca²⁺- release-activated Ca²⁺) channels in immune and non-excitable cells. Under physiological conditions, the intramolecular auto-inhibitions in STIM1 C- and STIM1 N-termini play essential roles in keeping STIM1 in an inactive state. However, the auto-inhibitory mechanism of the STIM1 C-terminus is still unclear. In the present study, we first predicted a short inhibitory domain (residues 310-317) in human STIM1 that might determine the different localizations of human STIM1 from Caenorhabditis elegans STIM1 in resting cells. Next, we confirmed the prediction and further identified an aromatic amino acid residue, Tyr³¹⁶, that played a crucial role in maintaining STIM1 in a closed conformation in quiescent cells. Full-length STIM1-Y316A formed constitutive clusters near the plasma membrane and activated the CRAC channel in the resting state when co-expressed with Orai1. The introduction of a Y316A mutation caused the higher-order oligomerization of the in vitro purified STIM1 fragment containing both the auto-inhibitory domain and CAD(CRAC-activating domain).We propose that the Tyr³¹⁶ residue may be involved in the auto-inhibitory mechanism of the STIM1 C-terminus in the quiescent state. This inhibition could be achieved either by interacting with the CAD using hydrogen and/or hydrophobic bonds, or by an intermolecular interaction using repulsive forces, which maintained a dimeric STIM1. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/23795811/An_aromatic_amino_acid_in_the_coiled_coil_1_domain_plays_a_crucial_role_in_the_auto_inhibitory_mechanism_of_STIM1_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20130292 DB - PRIME DP - Unbound Medicine ER -