Insights into the key determinants of membrane protein topology enable the identification of new monotopic folds

ELife
Sonya EntovaBarbara Imperiali

Abstract

Monotopic membrane proteins integrate into the lipid bilayer via reentrant hydrophobic domains that enter and exit on a single face of the membrane. Whereas many membrane-spanning proteins have been structurally characterized and transmembrane topologies can be predicted computationally, relatively little is known about the determinants of membrane topology in monotopic proteins. Recently, we reported the X-ray structure determination of PglC, a full-length monotopic membrane protein with phosphoglycosyl transferase (PGT) activity. The definition of this unique structure has prompted in vivo, biochemical, and computational analyses to understand and define key motifs that contribute to the membrane topology and to provide insight into the dynamics of the enzyme in a lipid bilayer environment. Using the new information gained from studies on the PGT superfamily we demonstrate that two motifs exemplify principles of topology determination that can be applied to the identification of reentrant domains among diverse monotopic proteins of interest.

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Citations

May 31, 2020·The Journal of Biological Chemistry·Krista M ArmbrusterTimothy C Meredith
Dec 19, 2020·FEMS Microbiology Reviews·Tong SuLok-To Sham
Jan 22, 2021·Proceedings of the National Academy of Sciences of the United States of America·Katherine H O'TooleKaren N Allen
Oct 28, 2020·Nature Structural & Molecular Biology·Shintaro MaedaTakanori Otomo
Nov 18, 2020·Nature Chemical Biology·Milka DoktorovaIlya Levental
Dec 14, 2019·Cell Chemical Biology·Jean-Marie SwiecickiBarbara Imperiali
Aug 23, 2019·Journal of Chemical Theory and Computation·Irene MarzuoliFranca Fraternali

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Methods Mentioned

BETA
X-ray
circular dichroism
thermal shift
crosslinking studies
Fluorescence
peptide folding
acylation
PCR

Software Mentioned

Quikchange
PyMol
AmberTools15
Image Lab
Leap
SCAM
cpptraj
Membranome
GraphPad
Graphpad Prism

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