Exploring the kinetics of the interactions controlling the gating of the Ca2+-release activated Ca2+ channel
Calcium- release activated calcium channels (ORAI) are essential for sustained cytosol [Ca2+] elevation which is required for T cell activation and adaptive immunity. Upon ER luminal Ca2+ depletion, ER Ca2+ sensor STIM1 aggregates and translocates to the ER-PM junction, where it binds and activates...
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| Format: | Final Year Project |
| Language: | English |
| Published: |
2011
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| Online Access: | http://hdl.handle.net/10356/44746 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | Calcium- release activated calcium channels (ORAI) are essential for sustained cytosol [Ca2+] elevation which is required for T cell activation and adaptive immunity. Upon ER luminal Ca2+ depletion, ER Ca2+ sensor STIM1 aggregates and translocates to the ER-PM junction, where it binds and activates ORAI1 channel. But the fundamental issue regarding the kinetics of STIM1-ORAI1 interaction is unresolved. Here we use surface plasmon resonance technique to study STIM1-ORAI1 binding kinetics, and size exclusion chromatography coupled with light scattering technique to study STIM1 aggregation via in vitro assays. Our results suggest a possible gating mechanism of ORAI1 channel: coiled-coil 1 domain of STIM1 holds it to ORAI1 channel while its coiled-coil 2 and coiled-coil 3 domains interact with and thus opening ORAI1 channel in an on and off fashion. |
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