Grob, Aurélien Anthony (2021) Structural and functional features of the SLC10 membrane protein transporters. PhD thesis, University of Warwick.

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Abstract

The solute carrier transporter family 10 (SLC10), comprising more than 50 members across plants, animals and bacteria, encodes for a multitude of fascinating influx transporters, playing distinct roles in the transport of bile acids, steroidal hormones, drugs, and many other unknown solutes.

SLC10A7, classified as an ”orphan transporter”, is a unique and significantly abnormal member of this family, exclusively seen to play a distinct role in the negative regulation of intracellular calcium homeostasis, among humans, mice, zebrafish and yeast. This PhD study attempted to primarily characterise the structural features of bacterial homologues of this unique ten transmembrane transporter, whilst functional traits were also investigated. Membrane protein overexpression, detergent solubilisation, thermostability investigations as well as optimised protein purifications, from a multitude of bacterial SLC10A7 homologues, have all provided significant novel findings, whilst protein crystallisation and 3D structure determination remain challenging.

The apical sodium dependent bile acid transporter (ASBT) is involved in the uptake and transport of bile acids in the enterohepatic circulation of the intestines. Novel structural studies of a nine transmembrane Leptospira biflexa ASBT bacterial homologue were characterised, with successful crystallisation optimisations yielding a 2.2°A crystal dataset. Along with functional thermostability and optimised purification studies, this novel transporter exhibits both structural and functional differences to previously crystallised bacterial ASBT homologues (ASBTNM and ASBTY f).

Together, both these projects further the knowledge of the functional and structural classifications of the SLC10 protein family. Chapter

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QH Natural history Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Carrier proteins, Biological transport, Bile acids -- Transport properties
Official Date:	December 2021
Dates:	Date Event December 2021 UNSPECIFIED
Institution:	University of Warwick
Theses Department:	School of Life Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Cameron, Alexander
Sponsors:	Biotechnology and Biological Sciences Research Council (Great Britain) ; Midlands Integrative Biosciences Training Partnership
Format of File:	pdf
Extent:	xviii, 236 leaves : illustrations
Language:	eng

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