期刊
ANNUAL REVIEW OF BIOPHYSICS
卷 51, 期 -, 页码 39-61出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-biophys-090821-083030
关键词
Markov state modeling; membrane transport; molecular dynamics simulations; rhodopsin; scramblase; TMEM16
类别
资金
- National Institutes of Health [R01 EY027969, R21 EY028314]
- HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute of Computational Biomedicine atWeill CornellMedical College
The rapid flip-flop of phospholipids across the two leaflets of biological membranes is crucial for many aspects of cellular life. G protein-coupled receptors (GPCRs), such as opsins, exhibit constitutive scramblase activity in vitro, with opsins scrambling lipids at a unitary rate of >100,000 per second. This review discusses the physiological significance of GPCR scramblase activity and its regulation in cells.
Rapid flip-flop of phospholipids across the two leaflets of biological membranes is crucial for many aspects of cellular life. The transport proteins that facilitate this process are classified as pump-like flippases and floppases and channel-like scramblases. Unexpectedly, Class A G protein-coupled receptors (GPCRs), a large class of signaling proteins exemplified by the visual receptor rhodopsin and its apoprotein opsin, are constitutively active as scramblases in vitro. In liposomes, opsin scrambles lipids at a unitary rate of >100,000 per second. Atomistic molecular dynamics simulations of opsin in a lipid membrane reveal conformational transitions that expose a polar groove between transmembrane helices 6 and 7. This groove enables transbilayer lipid movement, conceptualized as the swiping of a credit card (lipid) through a card reader (GPCR). Conformational changes that facilitate scrambling are distinct from those associated with GPCR signaling. In this review, we discuss the physiological significance of GPCR scramblase activity and the modes of its regulation in cells.
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