GPCRs (G-protein-coupled receptors) are the largest class of cell-surface receptors. They are the targets of many bio-active molecules and thus could be promising targets for drugs. However, our understanding of GPCR is restricted mainly due to the difficulties of their expression and/or purification as recombinant proteins. In this paper, our studies about chemokine receptor (CXCR1) are shown as a model case of the investigation of GPCR, and the prospects of this field of research are discussed.
Mitochondria are dynamic organelles that undergo cycles of homotypic fusion and fission, which are believed to play an important role in controlling organelle number, subcellular distribution, morphology, and ATP production. In mammals, mitochondrial fusion is essential for embryonic development and is controlled by the mitofusins, Mfn1 and Mfn2. Despite our increasing knowledge about importance of mitofusins, we have almost no understanding of how they function from a mechanistic perspective. Here we review our current molecular understanding of murine mitofusins, and discuss how mitofusins might mediate mitochondrial fusion.
Sodium ions are the most popular ions in body fluids, and the sodium and water homeostasis is essential for animal life. Although the presence of sensing system for the Na+ level in body fluids was postulated, its detail has long been an enigma. Recently we revealed that Nax, a family member of voltage-gated sodium channels, is involved in the monitoring of the level of sodium ions in body fluids and sodium/water intake behavior. Here we introduce our studies about the sodium sensor in the brain.
We have investigated the conformational and dynamical changes of plant-type ferredoxin (Fd) depending upon the redox state by 2D NMR spectroscopy and the three-dimensional structures of Fd, Fd:NADP+ reductase (FNR) and their complex by X-ray crystallography. These combined data allow us to discuss a molecular mechanism for the redox dependent change in the affinity of Fd with FNR, which is important in modulating redox metabolism in the cells, and also discuss the molecular property of Fd as an electron carrier in living cells.
Rotating waves underlie many life threatening cardiac arrhythmias. Cardiac chaos (fibrillation) can be controlled by applying a large damaging electric shock. It removes all waves, normal waves and reentries, in the entire heart. Anatomical reentries can be removed by anti-tachycardia pacing (ATP). To increase the success rate of ATP, it requires the knowledge of the position of the reentry. We show that the physics of electric field distribution between cardiac cells permits one to deliver an electric pulse exactly to the core of an anatomical reentry, without knowing its position. The energy needed is two orders less than defibrillation energy.