Kralt Annemarie, Carretta Marco, Mari Muriel, Reggiori Fulvio, Steen Anton, Poolman Bert, Veenhoff Liesbeth M
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.
Traffic. 2015 Feb;16(2):135-47. doi: 10.1111/tra.12243. Epub 2014 Dec 28.
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.
膜连接或接触位点是异源细胞器脂质双层的紧密关联。Ist2是一种驻留在内质网（ER）的跨膜蛋白，它介导了酿酒酵母中质膜（PM）与皮质内质网（cER）之间的关联。我们提出了一个问题，即Ist2中的何种结构跨越了质膜与皮质内质网之间长达30纳米的距离，并且我们注意到，将跨膜结构域与与质膜相互作用的皮质分选信号隔开的区域预计是内在无序的（ID）。在Ssy1中，一种先前未被描述为驻留在膜连接位点的蛋白质，我们识别出了与Ist2中相似的结构域组织。我们发现，Ist2和Ssy1在细胞周边的定位取决于质膜结合结构域、足够长度的ID连接区以及极有可能驻留在内质网中的跨膜结构域的存在。我们首次表明，一个ID氨基酸结构域跨越相邻的异源膜。ID结构域的长度和灵活性使其特别适合跨越较大距离，并且我们认为这种结构域结构在介导膜接触位点形成的蛋白质中更频繁地出现。
