Protein secretion domain

Wickner (1980) proposed an alternative mechanism of protein secretion, called the membrane trigger hypothesis. This model proposes that the signal sequence influences the precursor protein or a domain of the precursor to fold into a conformation that can spontaneously partition into the hydrophobic part of the bilayer. In prokaryotes, the membrane potential causes the protein to traverse the bilayer. The protein then regains a water-soluble conformation, and is expelled into the medium. Signal peptidase removes the signal sequence during or after this process. Thus, secretory proteins or domains are transported across the membrane posttranslationally without the aid of a proteinaceous secretory apparatus. An energy source, such as the membrane potential, is required for secretion. 

Examples of all three types of alternative RNA processing occur during sexual differentiation in Drosophila (see Figure 12-14). Commonly, one mRNA is produced from a complex transcription unit in some cell types, and an alternative mRNA is made in other cell types. For example, differences in RNA splicing of the primary fibronectin transcript in fibroblasts and hepatocytes determines whether or not the secreted protein Includes domains that adhere to cell surfaces (see Figure 4-15). 

SECRET domain VARV, ECTV, CPXV Secreted, protein domain fused to the TNFRs CrmB and CrmD, or expressed independently as three SCPs encoded by different genes, binds a limited set of CC and CXC chemokines, inhibits cell migration 42... 

The identification of the SECRET domain in five different poxvirus proteins is intr uit. This distribution may explain, in part, the variety of genes encoding TNFR homologues in poxvirus genomes, some of which (CrmB and CrmD) encode this additional chemokme-inhilntory activity. It may also provide the virus the abihty to differentially block chemokines involved in controllii distinct antiviral responses, inhibit chemokines at different sta of infection in the animal host or simultaneously inhibit chemokines and TNF. It is likely that as poxviruses with narrow host species specificity adapted to particular hosts (Le., VARY to humans or ECTV to mice), nes were selected to facilitate viral replication and transmission in each host. 

T7 protein. By constrast, the evasin family of CKBPs and the poxvirus-encoded SECRET domain show narrow binding specificity. CKBPs may interfere with chemokine-GAC interactions, disrupting the presenttttion of chemokines on the surface of endothelial cells and the formation of chemokine gradients, or may sequester chemokines and block the interaction of chemokines to specific receptors and the induction of cell migration. 

Sec7 Domain. The SECT protein was identified in a genetic screen of Saccharomyces cerevisiae mutants for defects in protein secretion (Achstetter et al., 1988). Structurally similar domains that were later recognized in other proteins involved in vesicular trafficking were referred as See domains and subsequently shown to be responsible for ARF activation (Morinaga et al., 1996 Peyroche et al., 1996) as well as its sensitivity to... 

AChE-R (in purple) Naturally rare, stress-induced variant, which lacks a hydrophobic domain and is incapable of binding to ColQ or PRiMA. Therefore, it remains soluble, and its secreted form shows greater mobility than AChE-S. AChE-R can intra-cellularly interact through its C-terminal tail with the Protein Kinase C Receptor RACK1, a scaffold protein which modifies multiple cellular processes. 

Semaphorins are secreted, membrane-associated or transmembrane proteins defined by the presence of a sema-phorin protein domain (Serna domain). In the mammalian system, more than 20 semaphorins have been identified which play important roles in a variety of tissues. The best characterized receptors for mediating semaphoiin effects are members of the neuropilin and plexin families of transmembrane proteins. Semaphoiin functions are best described in the regulation of neural development, angiogenesis, immunoregulation and cancer. 

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