The conformation of human phospholipid scramblase 1, as studied by infrared spectroscopy. Effects of calcium and detergent.

Autor: Andraka N; Unidad de Biofísica (CSIC, UPV/EHU) and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080 Bilbao, Spain., Sánchez-Magraner L; Unidad de Biofísica (CSIC, UPV/EHU) and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080 Bilbao, Spain., García-Pacios M; Unidad de Biofísica (CSIC, UPV/EHU) and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080 Bilbao, Spain., Goñi FM; Unidad de Biofísica (CSIC, UPV/EHU) and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080 Bilbao, Spain., Arrondo JL; Unidad de Biofísica (CSIC, UPV/EHU) and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080 Bilbao, Spain. Electronic address: joseluis.arrondo@ehu.es.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2017 May; Vol. 1859 (5), pp. 1019-1028. Date of Electronic Publication: 2017 Feb 24.
DOI: 10.1016/j.bbamem.2017.02.015
Abstrakt: Human phospholipid scramblase 1 (SCR) is a membrane protein that catalyzes the transmembrane (flip-flop) motion of phospholipids. It can also exist in a non membrane-bound form in the nucleus, where it modulates several aspects of gene expression. Catalysis of phospholipid flip-flop requires the presence of millimolar Ca 2+ , and occurs in the absence of ATP. Membrane-bound SCR contains a C-terminal α-helical domain embedded in the membrane bilayer. The latter domain can be removed giving rise to a stable truncated mutant SCRΔ that is devoid of scramblase activity. In order to improve our understanding of SCR structure infrared spectra have been recorded of both the native and truncated forms, and the effects of adding Ca 2+ , or removing detergent, or thermally denaturing the protein have been observed. Under all conditions the main structural component of SCR/SCRΔ is a β-sheet. Removing the C-terminal 28 aa residues, which anchor SCR to the membrane, leads to a change in tertiary structure and an increased structural flexibility. The main effect of Ca 2+ is an increase in the α/β ratio of secondary structure components, with a concomitant increase in the proportion of non-periodic structures. At least in SCRΔ, detergent (Zwittergent 3-12) decreases the structural flexibility, an effect somewhat opposite to that of increasing temperature. Thermal denaturation is affected by Ca 2+ , detergent, and by the presence or absence of the C-terminal domain, each of them influencing in different ways the denaturation pattern.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: