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Lipids shape the flat energetic landscape of the GLUT transporter cycle
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.ORCID-id: 0000-0001-7104-6442
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Biologiska vetenskaper
Forskningsämne
biokemi
Identifikatorer
URN: urn:nbn:se:su:diva-175419OAI: oai:DiVA.org:su-175419DiVA, id: diva2:1365895
Tillgänglig från: 2019-10-25 Skapad: 2019-10-25 Senast uppdaterad: 2019-11-01Bibliografiskt granskad
Ingår i avhandling
1. Establishing the mechanistic basis of sugar transport
Öppna denna publikation i ny flik eller fönster >>Establishing the mechanistic basis of sugar transport
2019 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Sugar is a vital molecule required for cell viability and homeostasis. Sugar is important for metabolic energy, energy storage, signaling, structure and osmolyte regulation. Transport of sugar represents an important physiological process. Specific membrane transporter families have evolved to mediate the transport of sugar across biological membranes. In this thesis, we describe our work leading to a better mechanistic understanding of two sugar transporter families, namely glucose (GLUT) transporters and nucleotide-sugar (NST) transporters.

Members of GLUT transporters, belonging to the Solute Carrier (SLC2) family, are involved in the uptake of various monosaccharides across the cellular membranes. Activity of different NSTs, belonging to the (SLC35) family, is crucial for the process of glycosylation by mediating the translocation of activated sugars from the cytoplasm into the lumen of either Golgi and/or ER organelles. GLUTs and NSTs families carry out transport processes fundamental to human physiology and pathophysiology. Despite the profound importance of GLUTs and NSTs in human health, comprehensive understanding of their architecture and mechanistic features with respect to determinants of substrate binding and allosteric coupling at the molecular level has remained elusive.

In this thesis, we address key functional and structural properties of GLUT and NST mediated sugar transport. We combine crystal structures with robust binding and transport assays as well as computational approaches. The role of lipids in fine-tuning the activity of transporters is also exemplified by demonstrating the effect of lipid composition in the transport activity of GLUTs using in-vitro proteoliposome assays. Our work has not only enhanced the current understanding of GLUT and NST function, but also developed themes and methods that are likely relevant to many types of small molecule transporters.

Ort, förlag, år, upplaga, sidor
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2019. s. 58
Nyckelord
membrane transport, transport energetics, nucleotide-sugar transporters, glucose transporters, malaria, cancer
Nationell ämneskategori
Biokemi och molekylärbiologi
Forskningsämne
biokemi
Identifikatorer
urn:nbn:se:su:diva-175422 (URN)978-91-7797-897-8 (ISBN)978-91-7797-898-5 (ISBN)
Disputation
2019-12-11, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (Engelska)
Opponent
Handledare
Anmärkning

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.

Tillgänglig från: 2019-11-18 Skapad: 2019-10-25 Senast uppdaterad: 2019-11-08Bibliografiskt granskad

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Qureshi, Abdul AzizSuades, AlbertDrew, David
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Institutionen för biokemi och biofysik
Biologiska vetenskaper

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