Cysteine residues of the mammalian GET receptor: Essential for tail-anchored protein insertion?

Schaefer, Moritz

dc.contributor.advisor	Schwappach, Blanche Prof. Dr.
dc.contributor.author	Schaefer, Moritz
dc.date.accessioned	2017-05-17T09:00:28Z
dc.date.available	2017-06-06T22:50:08Z
dc.date.issued	2017-05-17
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0023-3E49-D
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-6307
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	610	de
dc.title	Cysteine residues of the mammalian GET receptor: Essential for tail-anchored protein insertion?	de
dc.type	doctoralThesis	de
dc.contributor.referee	Thumm, Michael Prof. Dr.
dc.date.examination	2017-05-30
dc.description.abstracteng	Tail-anchored proteins integrate into lipid bilayers via a single transmembrane segment at their extreme C-terminus. The membrane insertion step is mediated by a heterodimeric receptor complex formed by WRB and CAML in higher eukaryotes and Get1 and Get2 in yeast. The transmembrane domains of the receptor complex form an integration site at the endoplasmic reticulum membrane and interact transiently with the transmembrane domain of an integrating TA protein prior to its membrane embedding. Cysteine residues are absent in yeast Get1 and Get2 whereas the mammalian homologues WRB and CAML contain three and five cysteines respectively. I aimed to investigate the role of the cysteine residues of WRB and CAML and test whether they are essential for TA protein targeting. Mutants of WRB and CAML in which the cysteine residues were mutated to serine were generated and I used a yeast-based complementation assay in which cells depleted of Get1 and Get2 were transformed with plasmids encoding either wild type or mutant WRB and CAML. Mutants were still able to create a receptor complex as assayed by yeast two-hybrid and did not impair the targeting of a substrate TA protein. Moreover, mutants rescued growth phenotypes of GET mutants confirming the formation of a functionally active receptor. In line with the absence of cysteines in the yeast GET receptor, cysteines in WRB and CAML seem to be not essential for TA protein targeting and may be required for potential still unknown regulation of TA protein targeting such as receptor stoichiometry, substrate quality control and chaperone function.	de
dc.contributor.coReferee	Oppermann, Martin Prof. Dr.
dc.subject.eng	GET	de
dc.subject.eng	Guided entry of tail-anchored proteins	de
dc.subject.eng	WRB	de
dc.subject.eng	CAML	de
dc.subject.eng	GET receptor	de
dc.subject.eng	Yeast two-hybrid	de
dc.subject.eng	redox regulation	de
dc.subject.eng	oxidative stress	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0023-3E49-D-5
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Medizin (PPN619874732)	de
dc.subject.gokfull	Physiologische Chemie	de
dc.subject.gokfull	Biochemie	de
dc.subject.gokfull	Pathobiochemie - Allgemein- und Gesamtdarstellungen	de
dc.description.embargoed	2017-06-06
dc.identifier.ppn	887658504

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