Abstract
The glycosyl carrier lipids, dolichylphosphate (C95-P) and undecapreylphosphate (C55-P) are key molecular players in the synthesis and translocation of complex glycoconjugates across cell membranes. The molecular mechanism of how these processes occur remains a mystery. Failure to completely catalyze C95-P-mediated N-linked protein glycosylation is lethal, as are defects in the C55-P-mediated synthesis of bacterial cell surface polymers. Our recent NMR studies have sought to understand the role these "super-lipids" play in biosynthetic and translocation pathways, which are of critical importance to problems in human biology and molecular medicine. The PIs can alter membrane structure by inducing in the lamellar phospholipids (PL) bilayer a non-lamellar or hexagonal (HexII) structure. Membrane proteins that bind PIs contain a transmembrane binding motif, designated a PI recognition sequence (PIRS). Herein we review our recent combination of 1H- and 31P NMR spectroscopy and energy minimized molecular modeling studies that have determined the preferred orientation of PIs in model phospholipids membranes. They also show that the addition of a PIRS peptide to nonlamellar membranes induced by the PIs can reverse the HexII phase back to a lamellar structure. Our molecular modeling calculations have also shown that as many as five PIRS peptides can bind to a single PI molecule. These findings lead to the hypothesis that the PI-induced HexII structure may have the potential of forming a membrane channel that could facilitate glycoconjugate translocation processes. This is an alternate hypothesis to the possible existence of hypothetical "flippases" to accomplish movement of hydrophilic sugar chains across hydrophobic membranes.
Keywords: nmr, glycobiology, glycosyltransferases, polyisoprenol (dolichol) structure, glycosyl translocation, polyisoprenyl recognition sequence peptides, polyisoprenol membrane orientation
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Books
In Vitro Propagation and Secondary Metabolite Production from Medicinal Plants: Current Trends (Part 2)
Micropropagation of Medicinal Plants
Software and Programming Tools in Pharmaceutical Research
Biotechnology and Drug Development for Targeting Human Diseases
In Vitro Propagation and Secondary Metabolite Production from Medicinal Plants: Current Trends (Part 1)
Molecular and Physiological Insights into Plant Stress Tolerance and Applications in Agriculture- Part 2
Micropropagation of Medicinal Plants
Genome Editing in Bacteria (Part 1)
Data Science for Agricultural Innovation and Productivity
Animal Models In Experimental Medicine
3
