title: Structural and Functional Insights into Small, Glutamine-Rich, Tetratricopeptide Repeat Protein Alpha.
abstract: The small glutamine-rich, tetratricopeptide repeat-containing protein alpha (SGTA) is an emerging player in the quality control of secretory and membrane proteins mislocalized to the cytosol, with established roles in tail-anchored (TA) membrane protein biogenesis. SGTA consists of three structural domains with individual functions, an N-terminal dimerization domain that assists protein sorting pathways, a central tetratricopeptide repeat (TPR) domain that mediates interactions with heat-shock proteins, proteasomal, and hormonal receptors, and viral proteins, and a C-terminal glutamine rich region that binds hydrophobic substrates. SGTA has been linked to viral lifecycles and hormone receptor signaling, with implications in the pathogenesis of various disease states. Thus far, a range of biophysical techniques have been employed to characterize SGTA structure in some detail, and to investigate its interactions with binding partners in different biological contexts. A complete description of SGTA structure, together with further investigation into its function as a co-chaperone involved quality control, could provide us with useful insights into its role in maintaining cellular proteostasis, and broaden our understanding of mechanisms underlying associated pathologies. This review describes how some structural features of SGTA have been elucidated, and what this has uncovered about its cellular functions. A brief background on the structure and function of SGTA is given, highlighting its importance to biomedicine and related fields. The current level of knowledge and what remains to be understood about the structure and function of SGTA is summarized, discussing the potential direction of future research.
authors.affiliation: Department of Chemistry, King's College London London, UK.
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Roberts
authors.affiliation: Department of Chemistry, King's College London London, UK.
authors.forename: Arjun
authors.initials: A
authors.lastname: Thapaliya
authors.affiliation: Department of Chemistry, King's College London London, UK.
authors.forename: Santiago
authors.initials: S
authors.lastname: Martínez-Lumbreras
authors.affiliation: Department of Chemistry, King's College London London, UK.
authors.forename: Ewelina M
authors.initials: EM
authors.lastname: Krysztofinska
authors.affiliation: Department of Chemistry, King's College London London, UK.
authors.forename: Rivka L
authors.initials: RL
authors.lastname: Isaacson
keywords: SGTA; biophysical techniques; cochaperones; protein sorting; quality control; structural biology