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
Current Protein & Peptide Science
Title: NMR Studies on How the Binding Complex of Polyisoprenol Recognition Sequence Peptides and Polyisoprenols Can Modulate Membrane Structure
Volume: 6 Issue: 5
Author(s): Guo-Ping Zhou and Frederic A. Troy II
Affiliation:
Keywords: nmr, glycobiology, glycosyltransferases, polyisoprenol (dolichol) structure, glycosyl translocation, polyisoprenyl recognition sequence peptides, polyisoprenol membrane orientation
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.
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Cite this article as:
Zhou Guo-Ping and Troy II A. Frederic, NMR Studies on How the Binding Complex of Polyisoprenol Recognition Sequence Peptides and Polyisoprenols Can Modulate Membrane Structure, Current Protein & Peptide Science 2005; 6 (5) . https://dx.doi.org/10.2174/138920305774329377
DOI https://dx.doi.org/10.2174/138920305774329377 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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