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61.
A signal sequence receptor in the endoplasmic reticulum membrane 总被引:3,自引:0,他引:3
Protein translocation across the endoplasmic reticulum (ER) membrane is triggered at several stages by information contained in the signal sequence. Initially, the signal sequence of a nascent secretory protein upon emergence from the ribosome is recognized by a polypeptide of relative molecular mass 54,000 (Mr54K) which is part of the signal recognition particle (SRP). Binding of SRP may induce a site-specific elongation arrest of translation in vitro. Attachment of the arrested translation complex to the ER membrane is mediated by the SRP-receptor (docking protein) and is accompanied by displacement of the SRP from both the ribosome and the signal sequence. We have investigated the fate of the signal sequence following the disengagement of SRP and its receptor by a crosslinking approach. We report here that the signal sequence of nascent preprolactin, after its release from the SRP, interacts with a newly discovered component, a signal sequence receptor (SSR), which is an integral, glycosylated protein of the rough ER membrane (Mr approximately 35K). 相似文献
62.
Jin Y Birlea SA Fain PR Ferrara TM Ben S Riccardi SL Cole JB Gowan K Holland PJ Bennett DC Luiten RM Wolkerstorfer A van der Veen JP Hartmann A Eichner S Schuler G van Geel N Lambert J Kemp EH Gawkrodger DJ Weetman AP Taïeb A Jouary T Ezzedine K Wallace MR McCormack WT Picardo M Leone G Overbeck A Silverberg NB Spritz RA 《Nature genetics》2012,44(6):676-680
We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.80 × 10(-8)), MC1R (P = 1.82 × 10(-13)), a region near TYR (P = 1.57 × 10(-13)), IFIH1 (P = 4.91 × 10(-15)), CD80 (P = 3.78 × 10(-10)), CLNK (P = 1.56 × 10(-8)), BACH2 (P = 2.53 × 10(-8)), SLA (P = 1.58 × 10(-8)), CASP7 (P = 3.56 × 10(-8)), CD44 (P = 1.78 × 10(-9)), IKZF4 (P = 2.75 × 10(-14)), SH2B3 (P = 3.54 × 10(-18)) and TOB2 (P = 6.81 × 10(-10)). Most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and the relationships among vitiligo, melanoma, and eye, skin and hair coloration. 相似文献
63.
The 2'-5' oligoadenylate synthetases (OAS) are interferon-induced antiviral enzymes that recognise virally produced dsRNA and initiate an RNA destabilisation within the infected cell. We compared the structure of OAS to that of poly adenosine polymerase (PAP) and the class I CCA-adding enzyme from Archeoglobus fulgidus (AfCCA). This comparison revealed a strong structural homology between the three enzyme families. In particular, the active sites of OAS and CCA class I enzymes are highly conserved. We conducted an extensive mutagenesis of amino acid residues within the putative active site in OAS, thereby identifying enzymatically important residues and confirming the common active site architecture for OAS and the AfCCA. Our findings also have profound implications for our understanding of the evolutionary origin of the OAS enzymes and suggest that the OAS proteins diverged from a common 3'-specific ancestor at the beginning of metazoan evolution. 相似文献