Show simple item record

dc.contributor.authorMartínez-Lumbreras, Santiago
dc.contributor.authorKrysztofinska, Ewelina M
dc.contributor.authorThapaliya, Arjun
dc.contributor.authorSpilotros, Alessandro
dc.contributor.authorMatak-Vinkovic, Dijana
dc.contributor.authorSalvadori, Enrico
dc.contributor.authorRoboti, Peristera
dc.contributor.authorNyathi, Yvonne
dc.contributor.authorMuench, Janina H
dc.contributor.authorRoessler, Maxie M
dc.contributor.authorSvergun, Dmitri I
dc.contributor.authorHigh, Stephen
dc.contributor.authorIsaacson, Rivka L
dc.date.accessioned2018-07-12T06:04:46Z
dc.date.available2018-07-12T06:04:46Z
dc.date.issued2018-07-11
dc.identifier.citationBMC Biology. 2018 Jul 11;16(1):76
dc.identifier.issn1741-7007
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/278038
dc.description.abstractBACKGROUND: Protein quality control mechanisms are essential for cell health and involve delivery of proteins to specific cellular compartments for recycling or degradation. In particular, stray hydrophobic proteins are captured in the aqueous cytosol by a co-chaperone, the small glutamine-rich, tetratricopeptide repeat-containing protein alpha (SGTA), which facilitates the correct targeting of tail-anchored membrane proteins, as well as the sorting of membrane and secretory proteins that mislocalize to the cytosol and endoplasmic reticulum-associated degradation. Full-length SGTA has an unusual elongated dimeric structure that has, until now, evaded detailed structural analysis. The C-terminal region of SGTA plays a key role in binding a broad range of hydrophobic substrates, yet in contrast to the well-characterized N-terminal and TPR domains, there is a lack of structural information on the C-terminal domain. In this study, we present new insights into the conformation and organization of distinct domains of SGTA and show that the C-terminal domain possesses a conserved region essential for substrate processing in vivo. RESULTS: We show that the C-terminal domain region is characterized by α-helical propensity and an intrinsic ability to dimerize independently of the N-terminal domain. Based on the properties of different regions of SGTA that are revealed using cell biology, NMR, SAXS, Native MS, and EPR, we observe that its C-terminal domain can dimerize in the full-length protein and propose that this reflects a closed conformation of the substrate-binding domain. CONCLUSION: Our results provide novel insights into the structural complexity of SGTA and provide a new basis for mechanistic studies of substrate binding and release at the C-terminal region.
dc.publisherSpringer Science and Business Media LLC
dc.titleStructural complexity of the co-chaperone SGTA: a conserved C-terminal region is implicated in dimerization and substrate quality control.
dc.typeJournal Article
dc.date.updated2018-07-12T06:04:38Z
dc.language.rfc3066en
dc.rights.holderIsaacson et al.
prism.publicationNameBMC Biol
dc.identifier.doi10.17863/CAM.25377
dcterms.dateAccepted2018-06-20
rioxxterms.versionofrecord10.1186/s12915-018-0542-3
dc.contributor.orcidIsaacson, Rivka L [0000-0002-9978-8904]
dc.identifier.eissn1741-7007
cam.issuedOnline2018-07-11


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record