Merzlyakov Mikhail, Hristova Kalina
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Methods Enzymol. 2008;450:107-27. doi: 10.1016/S0076-6879(08)03406-X.
Lateral interactions between hydrophobic transmembrane (TM) helices in membranes underlie the folding of multispan membrane proteins and signal transduction by receptor tyrosine kinases (RTKs). Quantitative measurements of dimerization energetics in membranes are required to uncover the physical principles behind these processes. Here, we overview how FRET measurements can be used to determine the thermodynamics of TM helix homo- and heterodimerization in vesicles and in supported bilayers. Such measurements can shed light on the molecular mechanism behind pathologies arising due to single-amino acid mutations in membrane proteins.
膜中疏水跨膜(TM)螺旋之间的横向相互作用是多跨膜蛋白折叠和受体酪氨酸激酶(RTK)信号转导的基础。需要对膜中二聚化能量进行定量测量,以揭示这些过程背后的物理原理。在这里,我们概述了如何使用荧光共振能量转移(FRET)测量来确定囊泡和支撑双层膜中TM螺旋同二聚化和异二聚化的热力学。此类测量可以揭示由于膜蛋白单氨基酸突变引起的病理背后的分子机制。