title: Topology mapping of insulin-regulated glucose transporter GLUT4 using computational biology.
abstract: The type 2 diabetes is increasing rapidly around the globe. The primary cause for this is insulin resistance due to the disruption of the insulin signal transduction mechanism. Insulin signal transduction stimulates glucose transport through the glucose transporter GLUT4, by promoting the exocytosis process. Understanding the structural topology of GLUT4 mechanism will increase our understanding of the dynamic activities about glucose transport and its regulation in the membrane environment. However, little is known about the topology of GLUT4. In this article, we have determined the amino acid composition, disulfide topology, structure conformation pattern of GLUT4. The amino acid composition portrays that leucine composition is the highest contributing to 15.5% among all other amino acids. Three cysteine residues such as Cys223, Cys361, and Cys363 were observed and the last two were associated with one disulfide bond formation. We have generated surface cavities to know the clefts/pockets on the surface of this protein that showed few irregular cavities placed mostly in the transmembrane-helical part. Besides, topology mapping of 12 transmembrane-helixes was done to predict N- and O-glycosylation sites and to show the highly glycosylated GLUT4 that includes both N- and O-glycosylation sites. Furthermore, hydrophobic segment and molecular charge distribution were analyzed. This article shows that bioinformatics tools can provide a rapid methodology to predict the topology of GLUT4. It also provides insights into the structural details and structural functioning relationships in the human GLUT4. The results can be of great help to advance future drug development research using GLUT4 as a target protein.
authors.affiliation: Department of Bioinformatics, School of Computer and Information Sciences, Galgotias University, Noida, India.
authors.forename: Chiranjib
authors.initials: C
authors.lastname: Chakraborty
authors.forename: Sanghamitra
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Ujjwal
authors.initials: U
authors.lastname: Maulik
authors.forename: Govindasamy
authors.initials: G
authors.lastname: Agoramoorthy
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D019295:Computational Biology; D030562:Databases, Protein; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007328:Insulin / Q000378:metabolism*; D008390:Markov Chains; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D005947:Glucose