COPII collar defines the boundary between ER and ER exit site and does not coat cargo containers

COPII and COPI mediate the formation of membrane vesicles translocating in opposite directions within the secretory pathway. Live-cell and electron microscopy revealed a novel mode of function for COPII during cargo export from the ER. COPII is recruited to membranes defining the boundary between the ER and ER exit sites, facilitating selective cargo concentration. Using direct observation of living cells, we monitored cargo selection processes, accumulation, and fission of COPII-free ERES membranes. CRISPR/Cas12a tagging, the RUSH system, and pharmaceutical and genetic perturbations of ER-Golgi transport demonstrated that the COPII coat remains bound to the ER–ERES boundary during protein export. Manipulation of the cargo-binding domain in COPII Sec24B prohibits cargo accumulation in ERES. These findings suggest a role for COPII in selecting and concentrating exported cargo rather than coating Golgi-bound carriers. These findings transform our understanding of coat proteins’ role in ER-to-Golgi transport.     

Peptides with Dual Antimicrobial-Anticancer Activity Derived from the N-terminal Region of H. pylori Ribosomal Protein L1 (RpL1)

International Journal of Peptide Research and Therapeutics - Whereas the traditional approaches of cancer therapy including radiotherapy, chemotherapy, and immunotherapy have failed to properly...     

The Role of Peptide-Based Tumor Vaccines on Cytokines of Adaptive Immunity: A Review

International Journal of Peptide Research and Therapeutics - Recently, peptide-based materials have been applied to solving many therapeutic problems and have shown particular efficacy as cancer...     

Computational Design and Analysis of a Multi-epitope Against Influenza A virus

International Journal of Peptide Research and Therapeutics - Influenza A viruses are among the most studied viruses, however no effective prevention against influenza infection has been developed....     

Fourfold paralogy regions on human HOX-bearing chromosomes: Role of ancient segmental duplications in the evolution of vertebrate genome

BackgroundSusumu Ohno’s idea that modern vertebrates are degenerate polyploids (concept referred as 2R hypothesis) has been the subject of intense debate for past four decades. It was proposed that intra-genomic synteny regions (paralogons) in human genome are remains of ancient polyploidization events that occurred early in the vertebrate history. The quadruplicated paralogon centered on human HOX clusters is taken as evidence that human HOX-bearing chromosomes were structured by two rounds of whole genome duplication (WGD) events.ResultsEvolutionary history of human HOX-bearing chromosomes (chromosomes 2/7/12/17) was evaluated by the phylogenetic analysis of multigene families with triplicated or quadruplicated distribution on these chromosomes. Topology comparison approach categorized the members of 44 families into four distinct co-duplicated groups. Distinct gene families belonging to a particular co-duplicated group, exhibit similar evolutionary history and hence have duplicated simultaneously, whereas genes of two distinct co-duplicated groups do not share their evolutionary history and have not duplicated in concert with each other.ConclusionThe recovery of co-duplicated groups suggests that “ancient segmental duplications and rearrangements” is the most rational model of evolutionary events that have generated the triplicated and quadruplicated paralogy regions seen on the human HOX-bearing chromosomes.     

Poxvirus antagonism of innate immunity by Bcl-2 fold proteins

Poxviruses have evolved numerous mechanisms to evade host innate immunity. Sensory pathways that are activated by Toll-like and nucleotide receptors, as well as innate cell death pathways, are both targets of antagonism by viral proteins. Recent structural, biochemical and functional studies of poxvirus proteins have identified a family of α-helical proteins that adopt a Bcl-2 fold despite highly divergent polypeptide sequences from cellular proteins that regulate apoptosis. These newly identified proteins have assumed new roles in antagonism of NF-κB and interferon signaling pathways and interfere with the release of pro-inflammatory cytokines. Structures of isolated viral proteins and their complexes with cellular targets provide insight into the diverse ways that the Bcl-2 scaffold can be exploited for antagonism of host immunity.     

Heat-Induced Conformational Unfolding of Fatty Acid-Free and Fatted Camel Serum Albumin: A Comparative Study

Albumin is a multifunctional non-glycosylated, negatively charged plasma protein, with extraordinary ligand-binding and transport properties, antioxidant functions, and enzymatic activities. Physiologically, albumin transports free fatty acids in plasma and contributes in maintaining colloid osmotic pressure. Recent progresses in using albumin as a versatile protein carrier for drug targeting and for improving the pharmacokinetic profile of peptide or protein-based drugs, increased the attempts for improving albumin stability. Studying the thermal stability of camel albumin may provide us not only new clues for designing recombinant albumins, but also molecular insights on camel physiology. This study aims to determine the thermal stability of camel albumin. Fatted camel serum albumin (FCSA) was purified from blood via combination of Cohn’s method and anion-exchange chromatography. Activated charcoal treatment was used to obtain defatted camel serum albumin (CSA). Fluorescence spectroscopy and differential scanning calorimetry (DSC) were used to study thermal denaturation of this protein. The set of fluorescence spectra were deconvoluted using the convex constraint analysis method (CCA). The results from deconvolution of fluorescence spectroscopy and DSC showed three and two components for CSA and FCSA, respectively. The bimodal DSC transition can be attributed to a crevice between domains I and II and formation of two independent thermodynamic domains. The crevice formation can be prevented by fatty acid binding between domains I and II. The calculated values of ?H _v/?H _cal, approximately 0.4 for CSA and near 1 for FCSA, confirmed the presence of at least one intermediate in thermal unfolding of CSA and the absence of the intermediate for FCSA. The obtained midpoint transition temperature (T _m) of FCSA was about 20 °C higher than that of CSA. Such enormous stabilizing effect may be attributed to the fact that fatty acid serves as glue which preserves different domains beside each other and prevents formation of the mentioned intermediate.     

The phosphatidylinositol‐transfer protein Nir2 binds phosphatidic acid and positively regulates phosphoinositide signalling

Phosphatidic acid (PA) and phosphoinositides are metabolically interconverted lipid second messengers that have central roles in many growth factor (GF)‐stimulated signalling pathways. Yet, little is known about the mechanisms that coordinate their production and downstream signalling. Here we show that the phosphatidylinositol (PI)‐transfer protein Nir2 translocates from the Golgi complex to the plasma membrane in response to GF stimulation. This translocation is triggered by PA formation and is mediated by its C‐terminal region that binds PA in vitro. We further show that depletion of Nir2 substantially reduces the PI(4,5)P2 levels at the plasma membrane and concomitantly GF‐stimulated PI(3,4,5)P3 production. Finally, we show that Nir2 positively regulates the MAPK and PI3K/AKT pathways. We propose that Nir2 through its PA‐binding capability and PI‐transfer activity can couple PA to phosphoinositide signalling, and possibly coordinates their local lipid metabolism and downstream signalling.     

Changes in anti-heat shock protein 27 antibody and C-reactive protein levels following cardiac surgery and their association with cardiac function in patients with cardiovascular disease

The relationship between serum anti-heat shock protein (Hsp)27 antibody and high sensitive C-reactive protein (hs-CRP) levels and indices of cardiac function were investigated in patients undergoing coronary artery bypass grafting (CABG) or heart valve replacement. The changes in anti-Hsp27 antibody titers and hs-CRP levels were compared among patients undergoing off-pump and on-pump CABG or valvular heart replacement. Fifty-three patients underwent off-pump, on-pump CABG, and heart valvular replacement in each group. Serum anti-Hsp27 titers and hs-CRP values were measured 24 h before and after the operation and at discharge. Echocardiography was performed before surgery and before discharge. The results were compared with values from 83 healthy controls. hs-CRP levels increased and anti-Hsp27 antibody decreased following surgery (P < 0.001 and P < 0.05, respectively), although these changes were independent of operative procedure (P = 0.361 and P = 0.120, respectively). Anti-Hsp27 antibody levels were higher at the time of discharge (P = 0.016). Only in coronary patients were anti-Hsp27 antibody levels negatively associated with E/E′ (r = −0.268, P = 0.022), a marker of pulmonary capillary wedge pressure. In conclusions, anti-Hsp27 antibody levels are associated with indices of cardiac function in coronary patients. Cardiopulmonary bypass had no significant effect on the induction of changes in anti-Hsp27 levels. Moreover, anti-Hsp27 antibody levels fell in all groups postoperatively; this may be due to the formation of immune complexes of antigen–antibody, and antibody levels were higher at the time of discharge.

Electronic supplementary material

The online version of this article (doi:10.1007/s12192-012-0358-y) contains supplementary material, which is available to authorized users.