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101.
De Pinto V Messina A Accardi R Aiello R Guarino F Tomasello MF Tommasino M Tasco G Casadio R Benz R De Giorgi F Ichas F Baker M Lawen A 《The Italian journal of biochemistry》2003,52(1):17-24
Mitochondrial porin or VDAC (Voltage Dependent Anion selective Channels) was identified for the first time in 1976, on the basis of the evolutionary similarity between the gram negative and mitochondrial outer membranes. Since this achievement VDAC has been extensively investigated: its functional features have been sharply defined upon reconstitution in artificial membranes and its sequence has been determined in many genomes. Unfortunately the tertiary structure has not yet been solved, mainly because it proved to be very difficult to get suitable crystals. Despite this established knowledge, in the last few years this protein has attracted renewed interest. There are two main reasons for this interest: the discovery, in most eukaryotes, of a family of genes encoding VDAC isoforms and the claims of VDAC involvement in the intrinsic pathway of apoptosis and in particular in the mechanism of cytochrome c release from mitochondria. We can affirm that nowadays the eukaryotic porin (or VDAC) is studied in a more general cellular contest, looking at the interactions and integration with other molecules, since VDAC is in a crucial position in the cell, forming the main interface between the mitochondrial and the cellular metabolisms. In this minireview we will briefly focus our attention onto the following topics: 1) recent advances about the structure of VDAC; 2) the VDAC-related multigene families; 3) the presence, targeting and function of VDAC in various cell membranes. 相似文献
102.
A cellular receptor of human rhinovirus type 2, the very-low-density lipoprotein receptor,binds to two neighboring proteins of the viral capsid 总被引:5,自引:0,他引:5 下载免费PDF全文
The very-low-density lipoprotein receptor (VLDL-R) is a receptor for the minor-group human rhinoviruses (HRVs). Only two of the eight binding repeats of the VLDL-R bind to HRV2, and their footprints describe an annulus on the dome at each fivefold axis. By studying the complex formed between a selection of soluble fragments of the VLDL-R and HRV2, we demonstrate that it is the second and third repeats that bind. We also show that artificial concatemers of the same repeat can bind to HRV2 with the same footprint as that for the native receptor. In a 16-A-resolution cryoelectron microscopy map of HRV2 in complex with the VLDL-R, the individual repeats are defined. The third repeat is strongly bound to charged and polar residues of the HI and BC loops of viral protein 1 (VP1), while the second repeat is more weakly bound to the neighboring VP1. The footprint of the strongly bound third repeat extends down the north side of the canyon. Since the receptor molecule can bind to two adjacent copies of VP1, we suggest that the bound receptor "staples" the VP1s together and must be detached before release of the RNA can occur. When the receptor is bound to neighboring sites on HRV2, steric hindrance prevents binding of the second repeat. 相似文献
103.
The E6 and E7 proteins of the cutaneous human papillomavirus type 38 display transforming properties 总被引:4,自引:0,他引:4 下载免费PDF全文
Caldeira S Zehbe I Accardi R Malanchi I Dong W Giarrè M de Villiers EM Filotico R Boukamp P Tommasino M 《Journal of virology》2003,77(3):2195-2206
Several studies have suggested the involvement of cutaneous human papillomaviruses (HPVs) in the development of nonmelanoma skin cancers. Here we have characterized the in vitro properties of E7 proteins of three cutaneous HPV types, 10, 20, and 38, which are frequently detected in skin specimens. We show that HPV38 E7 is able to inactivate the tumor suppressor pRb and induces loss of G(1)/S transition control, a key event in carcinogenesis. In contrast, HPV10 and HPV20 E7 proteins do not display these in vitro transforming activities. We also show that the two early proteins E6 and E7 of HPV38 are sufficient to corrupt the cell cycle and senescence programs in primary cells, inducing active and long-lasting proliferation of primary human keratinocytes, the natural host cells. Our study shows that E6 and E7 of this cutaneous HPV type have transforming activity in primary human cells, suggesting a role for HPV38 infection in skin carcinogenesis. In further support of such a role, we detected HPV38 DNA in approximately 50% of nonmelanoma skin cancers, but only in 10% of healthy skin specimens (P < 0.001). 相似文献
104.
ClC Cl(-) channels in endosomes, synaptosomes, lysosomes, and beta-cell insulin granules provide charge neutralization support for the functionally indispensable acidification of the luminal interior by electrogenic H(+)-ATPases (Jentsch, T. J., Stein, V., Weinreich, F., and Zdebik, A. A. (2002) Physiol. Rev. 82, 503-568). Regulation of ClC activity is, therefore, of widespread biological significance (Forgac, M. (1999) J. Biol. Chem. 274, 12951-12954). We now ascribe just such a regulatory function to the increases in cellular levels of inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P(4)) that inevitably accompany activation of the ubiquitous Ins(1,4,5)P(3) signaling pathway. We used confocal imaging to record insulin granule acidification in single mouse pancreatic beta-cells. Granule acidification was reduced by perfusion of single cells with 10 microm Ins(3,4,5,6)P(4) (the concentration following receptor activation), whereas at 1 microm ("resting" levels), Ins(3,4,5,6)P(4) was ineffective. This response to Ins(3,4,5,6)P(4) was not mimicked by 100 microm Ins(1,4,5,6)P(4) or by 100 microm Ins(1,3,4,5,6)P(5). Ins(3,4,5,6)P(4) did not affect granular H(+)-ATPase activity or H(+) leak, indicating that Ins(3,4,5,6)P(4) instead inhibited charge neutralization by ClC. The Ins(3,4,5,6)P(4)-mediated inhibition of vesicle acidification reduced exocytic release of insulin as determined by whole-cell capacitance recordings. This may impinge upon type 2 diabetes etiology. Regulatory control over vesicle acidification by this negative signaling pathway in other cell types should be considered. 相似文献
105.
Rosita Gabbianelli Giovanna Zolese Enrico Bertoli Giancarlo Falcioni 《European journal of biochemistry》2004,271(10):1971-1979
Circular dichroism (CD) spectra of two major hemoglobin components (Hb), HbI and HbIV, from Oncorhyncus mykiss (formerly Salmo irideus) trout were evaluated in the range 250-600 nm. HbI is characterized by a complete insensitivity to pH changes, while HbIV presents the Root effect. Both reduced [iron(II) or oxy] and oxidized (met) forms of the two proteins were studied at different pHs, 7.8 and 6.0, to obtain information about the pH effects on the structural features of these hemoglobins. Data obtained show that oxy and met-HbI are almost insensitive to pH decrease, remaining in the R conformational state also at low pH. On the contrary, the pH decrease induces similar structural changes, characteristics of ligand dissociation and R-->T transition, both in the reduced and in the oxidized HbIV. The structural changes, monitored by CD, are compared with the peroxidative activity of iron(II)-Hb and met-Hb forms and with the superoxide anion scavenger capacity of the proteins. 相似文献
106.
107.
Inactivation of erythrocyte GSH-peroxidase correlates with the rate of hemoglobin oxidation. The presence of superoxide dismutase and catalase only marginally reduces the rate of inactivation of the enzyme indicating that the loss of activity is not due to oxygen radicals produced during oxidation of hemoglobin. The inactivation of glutathione peroxidase is due by-and-large to the formation of hemichromes. 相似文献
108.
Luisa Calvanese Merlin Nanayakkara Rosita Aitoro Marina Sanseverino Anna Lucia Tornesello Lucia Falcigno Gabriella D'Auria Maria Vittoria Barone 《Journal of peptide science》2019,25(5)
Inflammation of intestinal tissue in patients affected by celiac disease (CD) originates from the adaptive and innate immune responses elicited by the undigested gliadin fragments through molecular mechanisms not yet completely described. Undigested A‐gliadin peptide P31‐43 is central to CD pathogenesis, entering enterocytes in vesicular compartments by endocytosis and inducing an innate immune response in CD intestinal mucosa. This study focused on the reasons why P31‐43 does not behave as adaptive immunogenic agent. Once obtained by NMR analysis, the three‐dimensional model of P31‐43 was used to implement a series of in silico experiments aimed to explore the ability of the peptide to interact with HLA‐DQ2 and the corresponding receptor onto T cells. Our results show that P31‐43 is a poor ligand for DQ2 and/or T‐cell receptor. This study was also aimed to investigate, from a structural point of view, the previous experimental findings by which P31‐43 is able to enhance the phosphorylation level of the protein ERK2, while some P31‐43 Ala‐mutants decrease or totally inhibit that process. The molecular models of P31‐43, P31‐43 P36A, and F37A mutants were used for in silico docking experiments onto the ERK2 structure. The experiments support the hypothesis that P31‐43 F37A works as an ERK2 phosphorylation inhibitor because it binds to the ERK2 phosphorylation site. This study reports on the structural properties of so far never NMR characterized gliadin peptides relevant in CD and explores details about their mechanisms of action. 相似文献
109.
CTCF interacts with and recruits the largest subunit of RNA polymerase II to CTCF target sites genome-wide 下载免费PDF全文
110.
Maille Baptiste Marlinge Marion Vairo Donato Mottola Giovanna Koutbi Linda Deharo Pierre Gastaldi Marguerite Gaudry Marine Guiol Claire Bottone Sara Mace Patrick Gueant Rosita Chefrour Mohamed Martinez Elsa Michelet Pierre Gueant Jean Louis Boussuges Alain Ruf Jean Fenouillet Emmanuel Deharo Jean Claude Guieu Régis Franceschi Frederic 《Purinergic signalling》2019,15(1):45-52
Purinergic Signalling - The mechanism of atrial fibrillation (AF) in patients with normal heart remains unclear. While exogenous adenosine can trigger AF, nothing is known about the behavior of... 相似文献