TY - JOUR
T1 - Essential Mycoplasma Glycolipid Synthase Adheres to the Cell Membrane by Means of an Amphipathic Helix
AU - Romero-García, Javier
AU - Biarnés, Xevi
AU - Planas, Antoni
N1 - Funding Information:
Work supported by grant BFU2016-77427-C2-1-R from MINECO, Spain, and 2017 SGR 727 from the Generalitat de Catalunya. J.R. acknowledges a predoctoral fellowship from IQS, and a contract from 2017 SGR 727. We thank Mercé Canal for the expression of the truncated proteins. We gratefully acknowledge access to computing facilities from RES-Red Española de Supercomputación.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Because of the lack of cell wall, Micoplasma species require a fine control of membrane fluidity and integrity. mg517 is an essential gene of Mycoplasma genitalium responsible for the biosynthesis of membrane glycoglycerolipids. It encodes for a unique glycosyltransferase (MG517) with processive activity, transferring activated glycosyl donors to either nude diacylglycerol or already glycosylated diacylglycerol. This dual activity, asserted to different enzymes in other species, is sensitive to and regulated by the presence of anionic lipid vesicles in vitro. We present here a computational model of the C-terminus domain of MG517 that complements a previous structural model of the N-terminus domain. By means of sequence analysis, molecular dynamics and metadynamics simulations, we have identified a short α-helix at the apical C-terminus of MG517 with clear amphipathic character. Binding to a membrane model is thermodynamically favored which suggests that this structural element guides the adhesion of MG517 to the cell membrane. We have experimentally verified that truncation of part of this helix causes a substantial reduction of glycoglycerolipids synthesis. The model proposes that MG517 recognizes and binds the diacylglycerol substrate embedded in the membrane by means of this α-helix at the C-terminus together with a previously identified binding pocket at the N-terminus.
AB - Because of the lack of cell wall, Micoplasma species require a fine control of membrane fluidity and integrity. mg517 is an essential gene of Mycoplasma genitalium responsible for the biosynthesis of membrane glycoglycerolipids. It encodes for a unique glycosyltransferase (MG517) with processive activity, transferring activated glycosyl donors to either nude diacylglycerol or already glycosylated diacylglycerol. This dual activity, asserted to different enzymes in other species, is sensitive to and regulated by the presence of anionic lipid vesicles in vitro. We present here a computational model of the C-terminus domain of MG517 that complements a previous structural model of the N-terminus domain. By means of sequence analysis, molecular dynamics and metadynamics simulations, we have identified a short α-helix at the apical C-terminus of MG517 with clear amphipathic character. Binding to a membrane model is thermodynamically favored which suggests that this structural element guides the adhesion of MG517 to the cell membrane. We have experimentally verified that truncation of part of this helix causes a substantial reduction of glycoglycerolipids synthesis. The model proposes that MG517 recognizes and binds the diacylglycerol substrate embedded in the membrane by means of this α-helix at the C-terminus together with a previously identified binding pocket at the N-terminus.
UR - http://www.scopus.com/inward/record.url?scp=85065559524&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-42970-9
DO - 10.1038/s41598-019-42970-9
M3 - Article
C2 - 31068620
AN - SCOPUS:85065559524
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 7085
ER -