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Conformational Regulation and Target-myristoyl Switch of Calcineurin B Homologous Protein 3
Abstract: Calcineurin B homologous protein 3 (CHP3) is an EF-hand Ca2+-binding protein involved in regulation of cancerogenesis, cardiac hypertrophy, and neuronal development through interactions with sodium/proton exchangers (NHEs) and signalling proteins. While the importance of Ca2+ binding and myristoylation for CHP3 function has been recognized, the underlying molecular mechanism remained elusive. In this study, we demonstrate that Ca2+ binding and myristoylation independently affect the conformation and functions of human CHP3. Ca2+ binding increased local flexibility and hydrophobicity of CHP3 indicative of an open conformation. The Ca2+-bound CHP3 exhibited a higher affinity for NHE1...
Stabilization of Membrane Topologies by Proteinaceous Remorin Scaffolds
Abstract: In plants, the topological organization of membranes has mainly been attributed to the cell wall and the cytoskeleton. Additionally, few proteins, such as plant-specific remorins have been shown to function as protein and lipid organizers. Root nodule symbiosis requires continuous membrane re-arrangements, with bacteria being finally released from infection threads into membrane-confined symbiosomes. We found that mutations in the symbiosis-specific SYMREM1 gene result in highly disorganized perimicrobial membranes. AlphaFold modelling and biochemical analyses reveal that SYMREM1 oligomerizes into antiparallel dimers and may form a higher-order membrane scaffolding structure. This ...
Calcium Affects CHP1 and CHP2 Conformation and Their Interaction with Sodium/proton Exchanger 1
Abstract: Calcineurin B homologous proteins (CHPs) belong to the EF-hand Ca2+-binding protein (EFCaBP) family. They have multiple important functions including the regulation of the Na+/H+ exchanger 1 (NHE1). The human isoforms CHP1 and CHP2 share high sequence similarity, but have distinct expression profiles with CHP2 levels for instance increased in malignant cells. These CHPs bind Ca2+ with high affinity. Biochemical data indicated that Ca2+ can regulate their functions. Experimental evidence for Ca2+-modulated structural changes was lacking. With a newly established fluorescent probe hydrophobicity (FPH) assay, we detected Ca2+-induced conformational changes in both CHPs. These changes ...
Heat Shock Proteins in Cancer
Heat shock proteins are emerging as important molecules in the development of cancer and as key targets in cancer therapy. These proteins enhance the growth of cancer cells and protect tumors from treatments such as drugs or surgery. However, new drugs have recently been developed particularly those targeting heat shock protein 90. As heat shock protein 90 functions to stabilize many of the oncogenes and growth promoting proteins in cancer cells, such drugs have broad specificity in many types of cancer cell and offer the possibility of evading the development of resistance through point mutation or use of compensatory pathways. Heat shock proteins have a further property that makes them tempting targets in cancer immunotherapy. These proteins have the ability to induce an inflammatory response when released in tumors and to carry tumor antigens to antigen presenting cells. They have thus become important components of anticancer vaccines. Overall, heat shock proteins are important new targets in molecular cancer therapy and can be approached in a number of contrasting approaches to therapy.
Bio-nanoimaging
Bio-Nanoimaging: Protein Misfolding & Aggregation provides a unique introduction to both novel and established nanoimaging techniques for visualization and characterization of misfolded and aggregated protein species. The book is divided into three sections covering: - Nanotechnology and nanoimaging technology, including cryoelectron microscopy of beta(2)-microglobulin, studying amyloidogensis by FRET; and scanning tunneling microscopy of protein deposits - Polymorphisms of protein misfolded and aggregated species, including fibrillar polymorphism, amyloid-like protofibrils, and insulin oligomers - Polymorphisms of misfolding and aggregation processes, including multiple pathways of lysozyme...
The Big Book on Small Heat Shock Proteins
Based upon a workshop entitled “The Small HSP World” held in Québec 2-5 October 2014. Twenty-five scientists provided chapters for the book. The chapters are from the best scientists currently working in this field. These colleagues include Arrigo, Benesch, Benjamin, Buchner-Haslbeck-Weinkauf, Benndorf, Boelens, Carra, Chang, Currie, Ecroyd, Emanuelsson, Fu, Garrido, Golenhofen, Gusev, Hightower, Kampinga, Lavoie, MacRae, Quinlan, Tanguay, Vierling, Vigh, Weeks and Wu. Briefly, the book starts with the structure of small heat shock proteins, moving to their functions and finishing with their involvement in diseases. Although this is quite broad, the structural aspect will be the unifying theme of the book.
The Murmuring Coast
This captivating tale is told in two parts. The first presents Lidia Jorge's version of a traditional story about a series of supposed incidents set in Beira, Mozambique. The events take place in the final years of Portugal's colonial African wars as an undisclosed narrator describes the military wedding of a young Portuguese ensign and an equally young bride. The wedding is followed by the mass poisoning of hundreds of native Africans and the arrival of a rain of locusts. The story ends grimly with the groom's suicide. Evita Lopo, the unnamed bride from the first part, narrates the remainder of the story. Twenty years have gone by and she reviews the past and questions the unidentified narrator's rendering of events in the first section. Evita's reminiscences destroy the credibility of the earlier story, and she supplies the reader with a great deal of information that the author of the previous account had suppressed or to which he or she merely alluded. It becomes apparent that betrayal and guilt have motivated all of the characters' actions.
The House of Stairs
The House of Stairs - an unputdownable crime classic from bestselling author Barbara Vine Lizzie hasn't seen her old friend, Bell, for some fourteen years, but when she spots her from a taxi in a London street she jumps out and pursues her despite 'all the terrible things' that passed between them. As Lizzie reveals those events, little by little, the women rekindle their friendship, with terrifying results ... 'This is the third psychological thriller by Ruth Rendell writing as Barbara Vine and when I say it surpasses the first two that's really saying something ... Vine has not only produced a quietly smouldering suspense novel but also presents an accurately atmospheric portrayal of Londo...
Lightning
Two perps--one a serial killer and the other a rapist who revisits his victims--test the limits of the 87th Precinct's detectives as they race to catch these maniacs loose on the city's streets. "McBain has the ability to make every character believable--which few writers these days can do." --Associated Press "McBain forces us to think twice about every character we meet...even those we thought we already knew." --New York Times Book Review
The Rhinemann Exchange
An explosive novel of suspense and intrigue set at the turning point of the Second World War. David Spaulding is the most feared and efficient Allied agent in wartime Europe. Expert, deadly and professional, he is also high on the Gestapo's 'most wanted' list. Now Spaulding has been selected by Allied Command to transact an undercover deal in Argentina involving top-secret Nazi scientific plans. The dealer is Erich Rhinemann, an exiled German Jew who is awaiting the end of the war with his millions in an impenetrable retreat near Buenos Aires. But there's something Spaulding doesn't know: the other side of the deal. And it involves the most bizarre, horrific intrigue of the Second World War...
