Related Experiment Video
Updated: Jul 14, 2026

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
Evolutionarily conserved hydrophobicity and sterics in TM3/TM4 balance Orai1 pore opening
Maximilian Fröhlich1, Tamara Radišković1, Valentina Hopl1
1JKU Life Science Center, Institute of Biophysics, Johannes Kepler University Linz, Linz, Austria.
Abstract:
The calcium (Ca2+) channel Orai1-the pore-forming subunit of the Ca2+ release-activated Ca2+ channel-is opened by its physiological activator, the endoplasmic reticulum (ER)-resident Ca2+ sensor stromal interaction molecule 1 (STIM1) upon ER Ca2+ store-depletion. STIM1 primarily engages the Orai1 C-terminus, relaying an activation signal from the channel periphery via all transmembrane (TM) domains to the Ca2+-conducting pore. We previously demonstrated that STIM1 coupling elicits conformational changes in the Orai1 TM3/TM4-interface inducing pore opening. Here, we reveal that a subtle balance of steric and hydrophobic interactions around V181 (TM3), F250 and F253 (TM4) is required for proper physiological function. We show that side chain volume and hydrophobicity in this region jointly determine not only the stability of the channel complex in the closed state, but also the extent of Ca2+ influx. In physiological settings, this fine-tuning around V181 permits sufficient activation, while preventing excessively large Ca2+ current.
Related Concept Videos
Membrane Fluidity
Membrane Fluidity
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Membrane Asymmetry Regulating Transporters
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Structure of Porins
