title: Intrinsically disordered linker and plasma membrane-binding motif sort Ist2 and Ssy1 to junctions.
abstract: Membrane junctions or contact sites are close associations of lipid bilayers of heterologous organelles. Ist2 is an endoplasmic reticulum (ER)-resident transmembrane protein that mediates associations between the plasma membrane (PM) and the cortical ER (cER) in baker's yeast. We asked the question what structure in Ist2 bridges the up to 30 nm distance between the PM and the cER and we noted that the region spacing the transmembrane domain from the cortical sorting signal interacting with the PM is predicted to be intrinsically disordered (ID). In Ssy1, a protein that was not previously described to reside at membrane junctions, we recognized a domain organization similar to that in Ist2. We found that the localization of both Ist2 and Ssy1 at the cell periphery depends on the presence of a PM-binding domain, an ID linker region of sufficient length and a transmembrane domain that most probably resides in the ER. We show for the first time that an ID amino acid domain bridges adjacent heterologous membranes. The length and flexibility of ID domains make them uniquely eligible for spanning large distances, and we suggest that this domain structure occurs more frequently in proteins that mediate the formation of membrane contact sites.
authors.affiliation: European Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Netherlands Proteomics Centre, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Kralt
authors.forename: Marco
authors.initials: M
authors.lastname: Carretta
authors.forename: Muriel
authors.initials: M
authors.lastname: Mari
authors.forename: Fulvio
authors.initials: F
authors.lastname: Reggiori
authors.forename: Anton
authors.initials: A
authors.lastname: Steen
authors.forename: Bert
authors.initials: B
authors.lastname: Poolman
authors.forename: Liesbeth M
authors.initials: LM
authors.lastname: Veenhoff
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C477782:IST2 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins; D008565:Membrane Proteins; C120527:SSY1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
keywords: amino acid signaling; endoplasmic reticulum; intrinsic disorder; membrane junction; membrane protein trafficking; plasma membrane