Extracellular Loop

FS activates the AC isoforms by binding in between the C1 and C2 domains and interacting with residues there with a combination of hydrophobic interactions and hydrogen bonding. These interactions are largely equally

Central region-C possess DNA-binding domain (DBD) which is said to be the most conserved region and possess similarity in their structure. DBD contains an important short motif known as P-box which is responsible for direct DNA interaction and detection of specificity for DNA-binding. DBD also possess additional sequences that are required for the homo or heterodimerization of nuclear receptors. A pair of zinc fingers present in domain C is critically responsible for DNA specific contacts and interaction. Domain D is the less conserved domain among nuclear receptors which acts as a flexible hinge in between two domains such as C (DBD) and E (LBD) domains. In addition, domain D possesses the nuclear localization signal (NLS) that regulates the sub cellular distribution of nuclear receptors. The E region contains ligand-binding domain (LBD) is

For example, -arrestins can mediate sustained ERK phosphorylation or protective mGluR signaling, which are G protein-independent processes (Emery 2010, Wang 2016). At the end of GPCR cycles, a regulator of G protein signaling (RGS) acts as GTPase activating proteins (GAPs), leading to GTP hydrolysis and reversing the receptor to an initial resting state (Sato 2015).

Myosin-Va (myoVa) is an actin-based molecular motor that delivers insulin granules to the plasma membrane for secretion from pancreatic β-cells1,2. This transport process is medically significant as the perturbation of this secretory process causes Type 2 diabetes3. The mechanism by which full-length myoVa (FL-myoVa) selects and binds to specific insulin granules and transports them to the plasma membrane for secretion is poorly understood. FL-MyoVa is recruited to insulin granules via a tripartite complex in which this motor protein is bound to a Rab effector protein (i.e., adapter) that links to Rab GTPase proteins (e.g., Rab27a) inserted in the granule membrane. Interestingly, there are at least four known adapter proteins expressed in β-cells, granuphilin A and B (Gran A and B), Rabphilin 3a and MyRIP, all of which bind FL-myoVa1,2.

The GPCR family all share a common structure and function-- they all have seven different protein segments that cross the membrane, and they detect molecules outside the cell and activate the signal inside the cell. Together with G-proteins, they cross the membrane 7 times,

The physiological function of each receptor subtype has not been established and is currently the subject of intensive investigation (1).

As reported previously (Nature 2015, Laub), phosphorylation of CtrA was observed in a manner dependent on ChpT and wild-type CckA∆TM (Fig. 3C). In contrast, CckA∆TM (S568W) failed to phosphotransfer to ChpT (Fig. 3C), indicating that the CckA S568 residue is prerequisite for the phosphotransfer reaction. This coincides well with the fact that S568 resides in the Rec domain and the idea that downregulation in the phosphotransfer activity of CckA could dampen the CtrA~P

One of the most important receptors in cell signalling is the trimeric (sinq kniga 596)G protein coupled receptor (GPCR). That is a receptor which has a surface part and an intracellular part (composed of 3 subunits a;b;y). GPCR pathway leads to the activation of another pathway group ERK (extracellular signal regulated kinases). This complex pathway is also regulated by phosphorylation (sinq kniga cell biology).

Figure 4.1 describes the distribution of the primary targets of drugs in the BNF, with human targets being the highest at 71%, followed by non-human targets at 17%, and non-specific targets at 12%. Analysis of the molecular target distribution of drugs with known human targets in the BNF reveals that receptors make up the highest group of drug targets, as shown in Figure 4.2. 59% of the human drug targets are receptors, and 33% of these are GPCRs. Enzymes are the second largest group of molecular targets in the human genome, making up 22% of all human drug targets.

The serum sodium levels appear to be higher than normal because the water is shifting from the ECF into the intracellular compartments (ICF).

Catalytic receptors are characteristically dimeric cell surface proteins that contain a single transmembrane domain which separates an extracellular ligand binding site and an intracellular enzymatic activity. Receptors with extrinsic tyrosine kinase activity and intrinsic protein serine/threonine kinase activity form minor subfamilies in this group2.

belong to the class of cell surface receptors that exhibit intrinsic tyrosine kinase activity. The

The structural support of heart is attributed to the extracellular matrix network of the heart. Pumping action of heart is due to the force generated by cardiomyocyte. The extracellular matrix network mainly consist of type I collagen with smaller amounts of type III collagen. This collagen network facilitates the transmission of a systolic force [9]. Tensile strength is provided by thick fibers mainly of type I collagen (85 % of total myocardial collagen). Type III collagen (11 % of the total collagen protein in the heart), forms thin fibers and is responsible for elasticity of the matrix network. Cardiac matrix network, morphologicaly can be subdivided into three constituents: the epimysium, perimysium and endomysium [10] (Figure 1). The entire cardiac muscle is enveloped by epimysium and is located on the endocardial and epicardial surface providing support for endothelial and mesothelial cells.

Similarly, paper III describes the GPCR complement in Saccoglossus kowalevskii. The study identified 260 unique GPCRs and classified 257 of them within the five main GPCR families; Glutamate (23), Rhodopsin (212), Adhesion (18), Frizzled (3) and Secretin (1). Intriguingly, this basal chordate contains several members of the Adhesion and Glutamate family members that are commonly found in vertebrates including humans. Comparisons with the human counterparts show that these sequences share a good pairwise sequence identity within the 7tm region and contain highly similar N-terminal domain architectures as well. We found 23 members belonging to the Glutamate family, including six GRMs-, eight GABABs-, three CASR- and one GPR158-like receptor.

Simultaneous to this contact, TNFRs create trimeric tips that slide into the gaps of the singular TNF structures. The contact between the TNF ligand and the TNFR causes a conformational change in the receptor --- as an effect, the inhibitory protein (IP) uncouples from the death domain located within the cell (Wajant and Pfizenmaier, 2003). The uncoupling of the IP creates an opportunity for a signal transducing adapter protein known as, “TNFR-type 1-associated Death domain protein” (TRADD), to react with the death domain and act as a location for consecutive binding of proteins. Ensuing the reaction between TRADD and the death domain, several new reactions can