Glycolipid Structure, Dynamics and Recognition in a Membrane Environment
EMSL Project ID
25434
Abstract
Eukaryotic cells depend on external surface markers, such as glycolipid molecules, to recognize and bind various other molecules as part of normal growth and maturation. As glycolipid molecules are situated on the outer surface of cells with their carbohydrate head-groups lying close to the membrane surface, they are usually also the first point of contact for viruses and microbes trying to invade healthy cells. Due to their critical role in disease, much effort has been directed at determining the three-dimensional structures of isolated carbohydrate head-groups; however, technical difficulties have generally prevented the study of the intact membrane-bound glycolipid. In particular, little is know about the orientation relative to membrane surface of the head-group. Head-group presentation can alter the glycans ability to interact with other molecules and is as important as its three-dimensional shape. We will use a combination of atomic-resolution structures derived from molecular dynamics simulations of glycolipids bound to lipid bilayers, and orientational dipolar coupling data from NMR spectroscopy of glycolipid-containing bicelles, to establish the orientation, conformation and dynamic properties of representative glycolipids. With experimentally verified glycolipid conformations, we will then investigate interactions between protein ligands and glycolipids through molecular dynamics ligand-receptor simulations. To date, experimental difficulties in resolving structures of glycolipids in biologically relevant environments has impeded our understanding of this fundamental biological and pathological process. This investigation aims to overcome this obstacle providing a method that integrates experimental (NMR) data and molecular dynamics simulations to predict three-dimensional structure and orientation of glycolipid molecules at the surface of cells.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2007-06-14
End Date
2009-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members