Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bergsmann, J; Derler, I; Muik, M; Frischauf, I; Fahrner, M; Pollheimer, P; Schwarzinger, C; Gruber, HJ; Groschner, K; Romanin, C.
Molecular determinants within N terminus of Orai3 protein that control channel activation and gating.
J Biol Chem. 2011; 286(36): 31565-31575.
Doi: 10.1074/jbc.M111.227546
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- Groschner Klaus
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- Abstract:
- STIM1 and Orai represent the key components of Ca(2+) release-activated Ca(2+) channels. Activation of Orai channels requires coupling of the C terminus of STIM1 to the N and C termini of Orai. Although the latter appears to be central in the interaction with STIM1, the role of the N terminus and particularly of the conserved region close to the first transmembrane sequence is less well understood. Here, we investigated in detail the functional role of this conserved region in Orai3 by stepwise deletions. Molecular determinants were mapped for the two modes of Orai3 activation via STIM1 or 2-aminoethoxydiphenyl borate (2-APB) and for current gating characteristics. Increasing N-terminal truncations revealed a progressive decrease of the specific fast inactivation of Orai3 concomitant with diminished binding to calmodulin. STIM1-dependent activation of Orai3 was maintained as long as the second half of this conserved N-terminal domain was present. Further truncations abolished it, whereas Orai3 stimulation via 2-APB was partially retained. In aggregate, the N-terminal conserved region plays a multifaceted role in Orai3 current gating with distinct structural requirements for STIM1- and 2-APB-stimulated activation.
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium Channels - chemistry Calcium Channels - metabolism
- Conserved Sequence -
- Humans -
- Ion Channel Gating -
- Membrane Proteins - metabolism Membrane Proteins - physiology
- Neoplasm Proteins - metabolism Neoplasm Proteins - physiology
- Sequence Deletion -