Structural basis for substrate specificity and regulation of nucleotide sugar transporters in the lipid bilayer

October 11, 2019

Parker, J., Corey, R., Stansfeld, P., et al.

Nature Communications 2019, vol: 10 doi: 10.1038/s41467-019-12673-w

Abstract

Nucleotide sugars are the activated form of monosaccharides used by glycosyltransferases during glycosylation. In eukaryotes the SLC35 family of solute carriers are responsible for their selective uptake into the Endoplasmic Reticulum or Golgi apparatus. The structure of the yeast GDP-mannose transporter, Vrg4, revealed a requirement for short chain lipids and a marked difference in transport rate between the nucleotide sugar and nucleoside monophosphate, suggesting a complex network of regulatory elements control transport into these organelles. Here we report the crystal structure of the GMP bound complex of Vrg4, revealing the molecular basis for GMP recognition and transport. Molecular dynamics, combined with biochemical analysis, reveal a lipid mediated dimer interface and mechanism for coordinating structural rearrangements during transport. Together these results provide further insight into how SLC35 family transporters function within the secretory pathway and sheds light onto the role that membrane lipids play in regulating transport across the membrane.

View Publication

Topics: Prometheus, nanoDSF, Membrane Proteins, Publications

Previous Article
Lipid-like peptides can stabilize integral membrane proteins for biophysical and structural studies
Lipid-like peptides can stabilize integral membrane proteins for biophysical and structural studies

Up next
Membrane (and soluble) protein stability and binding measurements in the lipid cubic phase using label-free DSF
Membrane (and soluble) protein stability and binding measurements in the lipid cubic phase using label-free DSF

Working with tricky membrane proteins?

NanoTemper tools can help

Find out how
×

Sign up to receive
the latest NanoTemper news, product updates, event announcements and more

First Name
Last Name
Company Name
Country
State
Province
State
Region
State
Canton
Agree to Subscribe & Privacy Policy*
*I have fully read, understood and agree to the Privacy Policy. I accept the storing and processing of my personal data by NanoTemper as described in the Privacy Policy.

By completing this form, you provide us consent to contact you with educational content, news and information about our products, services and events. You may unsubscribe at any time.
Thank you!
Error - something went wrong!