Proteins transmembrane domain

FIGURE 11-8 Integral membrane proteins. For known proteins of the plasma membrane, the spatial relationships of protein domains to the lipid bilayer fall into six categories. Types I and II have only one transmembrane helix the amino-terminal domain is outside the cell in type I proteins and inside in type II. Type III proteins have multiple transmembrane helices in a single polypeptide. In type IV proteins, transmembrane domains of several different polypeptides assemble to form a channel through the membrane. Type V proteins are held to the bilayer primarily by covalently linked lipids (see Fig. 11-14), and type VI proteins have both transmembrane helices and lipid (GPI) anchors. 

The first example of a high resolution solid-state 2D N PISEMA NMR spectrum has been reported for a transmembrane peptide aligned using hydrated cylindrical lipid bilayers formed inside nanoporous anodic aluminum oxide substrates. Using N and P NMR spectra, both the phospholipids and the protein transmembrane domain were shown to be uniformly aligned in the nanopores. 

The ANP leceptoi exists in two forms, ANP and ANPg, both of which have been cloned. These membrane-bound guanylate cyclases have a single transmembrane domain, an intracellular protein kinase-like domain, and a catalytic cyclase domain, activation of which results in the accumulation of cychc guanosine monophosphate (cGMP). A third receptor subtype (ANP ) has been identified that does not have intrinsic guanylate cyclase activity and may play a role in the clearance of ANP. 

FIGURE 21.11 The structure of UQ-cyt c reductase, also known as the cytochrome hci complex. The alpha helices of cytochrome b (pale green) define the transmembrane domain of the protein. The bottom of the structure as shown extends approximately 75 A into the mitochondrial matrix, and die top of the structure as shown extends about 38 A into the intermembrane space. (Photograph kindly provided by Di Xia and Johann Deismhofer [From Xia, D., Yn, C.-A., Kim, H., Xia,J-Z., Kachnrin, A. M., Zhang, L., Yn,... 

Foord, S. M., and Marshall, F. H. (1999). RAMPS Accessory proteins for seven transmembrane domain receptors. Trends Pharmacol. Sci. 20 184-187. 

Most ABC-transporters, especially those located in the plasma membrane, are phosphorylated and glycosylated transmembrane proteins of different molecular weights (e.g., P-gp 170 kDa MRP2 190 kDa BCRP 72 kDa). Topologically, most ABC-transporter show a similar structure they are organized in two transmembrane domains (TMD), each consisting of six... 

The breast cancer resistance protein (BCRP) belongs to the G-branch of the ABC-transporter family (ABCG2). In contrast to most other ABC-proteins, BCRP consists of only one transmembrane domain (TDM) with one nucleotide binding fold (NBF) at its C-terminus. Because of this structural characteristic BCRP as well as other ABC-transporters with only one TMD are termed half transporters. To achieve functional activity these transporters have to form hetero- or homodimers. BCRP is involved in the multidrug resistance of certain tumors and transports endogenous compounds like cholesterol and steroid hormones. 

Cadherins (Calcium-dependent adhesion proteins) are transmembrane proteins, which consist of an extracellular domain composed of cadherin-repeats, a transmembrane domain, and a cytoplasmic domain that interacts with catenins and/or other cytoplasmic proteins. 

Several nonconventional cadherins that contain cadherin repeats have been described but they have specific features not found in the classical cadherins [1]. The cadherin Flamingo, originally detected in Drosophila, contains seven transmembrane segments and in this respect resembles G protein-coupled receptors. The extracellular domain of Flamingo and its mammalian homologs is composed of cadherin repeats as well as EGF-like and laminin motifs. The seven transmembrane span cadherins have a role in homotypic cell interactions and in the establishment of cell polarity. The FAT-related cadherins are characterized by a large number of cadherin repeats (34 in FAT and 27 in dachsous). Their cytoplasmic domains can bind to catenins. T- (=truncated-)cadherin differs from other cadherins in that it has no transmembrane domain but is attached to the cell membrane via a glycosylpho-sphatidylinositol anchor. 

Heptahelical domains are protein modules found in all known G-protein coupled receptors, made up of seven transmembrane helices interconnected by three extra and three intracellular loops. For most G-protein coupled receptors activated by small ligands, the binding site is located in a cavity formed by transmembrane domains 3, 5, 6 and 7. 

The three selectins are related both structurally and functionally. They are transmembrane proteins, with an N-terminal C-type actin domain, followed by an EGF repeat and a variable number of complement control protein (CCP) domains. Selectins bind carbohydrates, which are present in various glycoproteins. 

SNAREs is an acronym for soluble NSF acceptor protein receptors. They are a superfamily of small and mostly membrane-bound proteins that are distinguished by the presence of a conserved stretch of 60 amino acids referred to as a SNARE motif. With few exceptions, a single transmembrane domain is located adjacent to the SNARE motif at the C-terminal end. Many SNAREs possess in addition an independently folded N-terminal domain whose structures are more diverse. 

Somatostatin is a regulatory cyclic peptide, which has originally been described as a hypothalamic growth hormone release-inhibiting factor. It is produced throughout the central nervous system (CNS) as well as in secretoty cells of the periphery and mediates its regulatory functions on cellular processes such as neurotransmission, smooth muscle contraction, secretion and cell proliferation via a family of seven transmembrane domain G-protein-coupled receptors termed sstx 5. 

---