caa a22 4500 477118968 CHVBK 20180405111630.0 cr unu---uuuuu 170330e19960601xx s 000 0 eng 10.1007/BF00226059 doi (NATIONALLICENCE)springer-10.1007/BF00226059 Co-translational effects of temperature on membrane insertion and orientation of P-glycoprotein sequences [Elektronische Daten] [Jian-Ting Zhang, Crispina Chong] P-glycoprotein (pgp) is a membrane transport protein that causes multidrug resistance (MDR) by actively extruding a wide variety of cytotoxic agents out of cells. It may also function as a peptide transporter, a volume-regulated chloride channel, and an ATP channel. Previously, it has been shown that hamster pgp1 Pgp is expressed in more than one topological form and that the generation of these structures is modulated by charged amino acids flanking the predicted transmembrane (TM) segments 3 and 4 and by soluble cytoplasmic factors. Different topological structures of Pgp may be related to its different functions. In this study, we examined the effects of translation temperature on the membrane insertion process and the topologies of Pgp. Using the rabbit reticulocyte lysate expression system, we showed that translation at different temperatures affects the membrane insertion and orientation of the putative TM3 and TM4 of hamster pgp1 Pgp in a co-translational manner. This observation suggests that the membrane insertion process of TM3 and TM4 of Pgp molecules may involve a protein conducting channel and/or the interaction between TM3 and TM4, which act in a temperature sensitive manner. We speculate that manipulating temperature may provide a way to understand the structure-function relationship of Pgp and help overcome Pgp-related multidrug resistance of cancer cells. Kluwer Academic Publishers, 1996 multidrug resistance nationallicence in vitro translation nationallicence thermal therapy nationallicence P-glycoprotein nationallicence topology, CFTR nationallicence Pgp : P-glycoprotein nationallicence MDR : multidrug resistance nationallicence ABC : ATP-binding cassette nationallicence RRL : rabbit reticulocyte lysate nationallicence TM : transmembrane nationallicence RM : rough microsomes nationallicence ER : endoplasmic reticulum nationallicence Zhang Jian-Ting Department of Physiology and Biophysics, University of Texas Medical Branch, 77555-0641, Galveston, Texas, USA aut Chong Crispina Department of Physiology and Biophysics, University of Texas Medical Branch, 77555-0641, Galveston, Texas, USA aut Molecular and Cellular Biochemistry Kluwer Academic Publishers 159/1(1996-06-01), 25-31 0300-8177 159:1<25 1996 159 11010 https://doi.org/10.1007/BF00226059 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00226059 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Jian-Ting Department of Physiology and Biophysics, University of Texas Medical Branch, 77555-0641, Galveston, Texas, USA aut NATIONALLICENCE 700 1- Chong Crispina Department of Physiology and Biophysics, University of Texas Medical Branch, 77555-0641, Galveston, Texas, USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers 159/1(1996-06-01), 25-31 0300-8177 159:1<25 1996 159 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer