Polytopic membrane proteins

Figure 46-5. Variations in the way in which proteins are inserted into membranes. This schematic representation, which illustrates a number of possible orientations, shows the segments of the proteins within the membrane as a-helicesand the other segments as lines. The LDL receptor, which crosses the membrane once and has its amino terminal on the exterior, is called a type I transmembrane protein. The asialoglycoprotein receptor, which also crosses the membrane once but has its carboxyl terminal on the exterior, is called a type II transmembrane protein. The various transporters indicated (eg, glucose) cross the membrane a number of times and are called type III transmembrane proteins they are also referred to as polytopic membrane proteins. (N, amino terminal C, carboxyl terminal.) (Adapted, with permission, from Wickner WT, Lodish HF Multiple mechanisms of protein insertion into and across membranes. Science 1985 230 400. Copyright 1985 by the American Association for the Advancement of Science.)...

Synaptobrevins (VAMPs) Synaptogyrin Synaptophysins PKA but diverge C-terminally. Synapsins Ia/b contain C-terminal phosphorylation sites for CaMKII and CDK 5. Interact with microfilaments, neurofilaments, microtubules, SH3 domains, calmodulin and annexin VI in vitro. Small-membrane proteins that are cleaved by tetanus toxin and by botulinum toxins B, D, F and G. Polytopic membrane protein that is tyrosine-phosphorylated. Function unknown. Polytopic membrane proteins, including synaptoporin, that are tyrosine-phosphorylated and bind to synaptobrevins. May regulate SNARE function... 

Jung, K., Voss, J., He, M., Hubbell, W. L., and Kaback, H. R. (1995) Engineering a metal binding site within a polytopic membrane protein, the lactose permease of Escherichia coli. Biochemistry 34, 6272-6277. 

Bogdanov, M., Heacock, P. N. and Dowhan, W. (2002). A polytopic membrane protein displays a reversible topology dependent on membrane lipid composition, EMBOJ., 21, 2107-2116. 

Bibi, E. (1998). The role of the ribosome-translocon complex in translation and assembly of polytopic membrane proteins. Trends Biochem. Sci. 23, 51—55. 

It is obvious that the biosynthesis of such a complex structure involves many proteins and steps. In fact, the anchor is synthesized in the ER, requiring a membrane-bound multistep pathway in which more than 20 gene products, mainly polytopic membrane proteins, take part." " The first two steps of the biosynthesis occur on the cytoplasmic site of the ER, and after flipping to the lumen of the ER the biosynthesis is completed. The GPI... 

Fig. 1.3 Classes of intrinsic membrane proteins, as defined by Blobel [29]. The peptides chains end in amino (N) and carboxy (C) termini. The disposition of the N- and C-termini differs for each class of membrane protein, only two membrane spannings are indicated for the polytopic class however, the number of membrane spannings is not limited for polytopic membrane proteins. (Reprinted from Fig. 1 of ref. 30 with permission from CRC Press.)...

Katragadda M, Alderfer JL, Yeagle PL (2001) Assembly of a Polytopic Membrane Protein Structure from the Solution Structures of Overlapping Peptide Fragments of Bacteriorhodopsin. Biophys J. 81(2) 1029-1036... 

Borel, A. C., and Simon, S. M. (1996a). Biogenesis of polytopic membrane proteins membrane segments assemble with translocation channels prior to membrane integration. Cell 85, 379-389. 

Monne, M., Galvelin, G., Nilsson, R., and von Heijne, G. (1999a). N-tail translocation in a eukaryotic polytopic membrane protein—synergy between neighboring transmembrane segments. Eur. J. Biochem. 263, 264-269. 

Javadpour, M. M., Eilers, M., Groesbeek, M., and Smith, S. O. (1999). Helix packing in polytopic membrane proteins role of glycine in transmembrane helix association. Biophys. J. 77, 1609-1618. 

PapD Membrane chaperones Absent from Eukarya Shr3p Gsf2p Pho68p Chs7p Present in some Prevention of aggregation of subunits of pUi Prevent aggregation of some integral polytopic membrane proteins... 

Solid-state NMR also can be applied to membrane proteins in lipid bilayers, and recent advancements in magic angle spinning solid-state NMR show promise for stmcture determination. Although the stmctures of small crystalline proteins (89) and membrane bound peptides (90) have been determined, the stmcture of a polytopic membrane protein has yet to be reported. The major necessity that is required to push the technique forward is the de novo sequential chemical shift assignment of the amino acid residues, and in the last few years, several groups have reported successful strategies (91, 92). 

Nakatsukasa, K., Huyer, G., Michaelis, S., and Brodsky, J.L. (2008) Dissecting the ER-associated degradation of a misfolded polytopic membrane protein. Cell, 132, 101-112. 

Polytopic membrane proteins are indispensable to the cellular uptake and homeostasis of many essential nutrients. During the past decade it has become clear that a vast... 

Table 8.3 Techniques for Studying Polytopic Membrane Protein Structure...

Bogdanov, M. and Dowhan, W., Phospholipid-assisted protein folding phosphatidyletha-nolamine is required at a late step of the conformational maturation of the polytopic membrane protein lactose permease, Embo J 17 (1998) 5255-5264. 

Nilsson, I. and von Heijne, G., Fine-tuning the topology of a polytopic membrane protein role of positively and negatively charged amino acids. Cell 62 (1990) 1135-1141. 

Zhang, J.T., Sequence requirements for membrane assembly of polytopic membrane proteins molecular dissection of the membrane insertion process and topogenesis of the human MDR3 P-glycoprotein, Mol Biol Cell 7 (1996) 1709-1721. 

Zhang, W., Bogdanov, M., Pi, J., Pittard, A.J. and Dowhan, W., Reversible topological organization within a polytopic membrane protein is governed by a change in membrane phospholipid composition, J Biol Chem 278 (2003) 50128-50135. 

A family of protein acyltransferases (PATs) is responsible for S-acylation of proteins in cells (S. Lobo, 2002 A. Roth, 2002) [8]. Members of this family are characterized by the presence of a cysteine-rich domain containing a DHHC (Asp-His-His-Cys) motif. PATs are polytopic membrane proteins with the putative catalytic DHHC motif localized to a cytoplasmic loop between transmembrane spans. Some PATs function alone whereas others, such as the yeast Ras PAT Erf2, require a cytoplasmic protein, Erf4, for activity. It is likely that particular classes of substrate have a dedicated PAT that accounts for most, if not all, of their S-acylation. For example, Swflp modifies SNARE proteins and other monotopic membrane proteins with a juxtamembrane cysteine residue. The yeast vacuolar protein Vac8 is mainly S-acylated by the vacuolar DHHC protein Pfa3 (J.E. Smotrys,... 

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