title: Structure and function of nucleotide sugar transporters: Current progress.
abstract: The proteomes of eukaryotes, bacteria and archaea are highly diverse due, in part, to the complex post-translational modification of protein glycosylation. The diversity of glycosylation in eukaryotes is reliant on nucleotide sugar transporters to translocate specific nucleotide sugars that are synthesised in the cytosol and nucleus, into the endoplasmic reticulum and Golgi apparatus where glycosylation reactions occur. Thirty years of research utilising multidisciplinary approaches has contributed to our current understanding of NST function and structure. In this review, the structure and function, with reference to various disease states, of several NSTs including the UDP-galactose, UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine, GDP-fucose, UDP-N-acetylglucosamine/UDP-glucose/GDP-mannose and CMP-sialic acid transporters will be described. Little is known regarding the exact structure of NSTs due to difficulties associated with crystallising membrane proteins. To date, no three-dimensional structure of any NST has been elucidated. What is known is based on computer predictions, mutagenesis experiments, epitope-tagging studies, in-vitro assays and phylogenetic analysis. In this regard the best-characterised NST to date is the CMP-sialic acid transporter (CST). Therefore in this review we will provide the current state-of-play with respect to the structure-function relationship of the (CST). In particular we have summarised work performed by a number groups detailing the affect of various mutations on CST transport activity, efficiency, and substrate specificity.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hadley
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Maggioni
authors.affiliation: Institut für Zelluläre Chemie, Zentrum Biochemie, Medizinische Hochschule Hannover, Carl-Neuberg Strasse 1, 30625 Hannover, Germany ; Laboratory of Genetic, Endocrine and Metabolic Diseases, Department of Neurology, Radboud University Medical Center, Geert Grooteplein Zuid 10 (route 830), Nijmegen, The Netherlands.
authors.forename: Angel
authors.initials: A
authors.lastname: Ashikov
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Day
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haselhorst
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia.
authors.forename: Joe
authors.initials: J
authors.lastname: Tiralongo
keywords: CMP-sialic acid transporter; Endoplasmic reticulum; Golgi apparatus; Nucleotide sugar transporters; STD NMR spectroscopy