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61.
Brian P. Ziemba Emma J. Murphy Hannah T. Edlin David N. M. Jones 《Protein science : a publication of the Protein Society》2013,22(1):11-21
Anopheles gambiae mosquitoes that transmit malaria are attracted to humans by the odor molecules that emanate from skin and sweat. Odorant binding proteins (OBPs) are the first component of the olfactory apparatus to interact with odorant molecules, and so present potential targets for preventing transmission of malaria by disrupting the normal olfactory responses of the insect. AgamOBP20 is one of a limited subset of OBPs that it is preferentially expressed in female mosquitoes and its expression is regulated by blood feeding and by the day/night light cycles that correlate with blood‐feeding behavior. Analysis of AgamOBP20 in solution reveals that the apo‐protein exhibits significant conformational heterogeneity but the binding of odorant molecules results in a significant conformational change, which is accompanied by a reduction in the conformational flexibility present in the protein. Crystal structures of the free and bound states reveal a novel pathway for entrance and exit of odorant molecules into the central‐binding pocket, and that the conformational changes associated with ligand binding are a result of rigid body domain motions in α‐helices 1, 4, and 5, which act as lids to the binding pocket. These structures provide new insights into the specific residues involved in the conformational adaptation to different odorants and have important implications in the selection and development of reagents targeted at disrupting normal OBP function. 相似文献
62.
The sequence dependence of DNA-protein interactions that allows proteins to find the correct reaction site also slows down the 1D diffusion of the protein along the DNA molecule, leading to the so-called “speed-stability paradox,” wherein fast diffusion along the DNA molecule is seemingly incompatible with stable targeting of the reaction site. Here, we develop diffusion-reaction models that use discrete and continuous Gaussian random 1D diffusion landscapes with or without a high-energy cut-off, and two-state models with a transition to and from a “searching” mode in which the protein diffuses rapidly without recognizing the target. We show the conditions under which such considerations lead to a predicted speed-up of the targeting process, and under which the presence of a “searching” mode in a two-state model is nearly equivalent to the existence of a high-energy cut-off in a one-state model. We also determine the conditions under which the search is either diffusion-limited or reaction-limited, and develop quantitative expressions for the rate of successful targeting as a function of the site-specific reaction rate, the roughness of the DNA-protein interaction potential, and the presence of a “searching” mode. In general, we find that a rough landscape is compatible with a fast search if the highest energy barriers can be avoided by “hopping” or by the protein transitioning to a lower-energy “searching” mode. We validate these predictions with the results of Brownian dynamics, kinetic Metropolis, and kinetic Monte Carlo simulations of the diffusion and targeting process, and apply these concepts to the case of T7 RNA polymerase searching for its target site on T7 DNA. 相似文献
63.
Hyun Seok Kim Saurabh Mendiratta Jiyeon Kim Chad Victor Pecot Jill E. Larsen Iryna Zubovych Bo Yeun Seo Jimi Kim Banu Eskiocak Hannah Chung Elizabeth McMillan Sherry Wu Jef De Brabander Kakajan Komurov Jason E. Toombs Shuguang Wei Michael Peyton Noelle Williams Adi F. Gazdar Bruce A. Posner Rolf A. Brekken Anil K. Sood Ralph J. Deberardinis Michael G. Roth John D. Minna Michael A. White 《Cell》2013
64.
Daopeng Yuan Anthony H. Keeble Richard G. Hibbert Stella Fabiane Hannah J. Gould James M. McDonnell Andrew J. Beavil Brian J. Sutton Balvinder Dhaliwal 《The Journal of biological chemistry》2013,288(30):21667-21677
Immunoglobulin E (IgE) antibodies play a fundamental role in allergic disease and are a target for therapeutic intervention. IgE functions principally through two receptors, FcϵRI and CD23 (FcϵRII). Minute amounts of allergen trigger mast cell or basophil degranulation by cross-linking IgE-bound FcϵRI, leading to an inflammatory response. The interaction between IgE and CD23 on B-cells regulates IgE synthesis. CD23 is unique among Ig receptors in that it belongs to the C-type (calcium-dependent) lectin-like superfamily. Although the interaction of CD23 with IgE is carbohydrate-independent, calcium has been reported to increase the affinity for IgE, but the structural basis for this activity has previously been unknown. We have determined the crystal structures of the human lectin-like head domain of CD23 in its Ca2+-free and Ca2+-bound forms, as well as the crystal structure of the Ca2+-bound head domain of CD23 in complex with a subfragment of IgE-Fc consisting of the dimer of Cϵ3 and Cϵ4 domains (Fcϵ3-4). Together with site-directed mutagenesis, the crystal structures of four Ca2+ ligand mutants, isothermal titration calorimetry, surface plasmon resonance, and stopped-flow analysis, we demonstrate that Ca2+ binds at the principal and evolutionarily conserved binding site in CD23. Ca2+ binding drives Pro-250, at the base of an IgE-binding loop (loop 4), from the trans to the cis configuration with a concomitant conformational change and ordering of residues in the loop. These Ca2+-induced structural changes in CD23 lead to additional interactions with IgE, a more entropically favorable interaction, and a 30-fold increase in affinity of a single head domain of CD23 for IgE. Taken together, these results suggest that binding of Ca2+ brings an extra degree of modulation to CD23 function. 相似文献
65.
Eric C. Hales Steven M. Orr Amanda Larson Gedman Jeffrey W. Taub Larry H. Matherly 《The Journal of biological chemistry》2013,288(31):22836-22848
66.
67.
In the interests of increasing fish production globally, alleviating global poverty, and income generation, marine aquaculture has seen worldwide expansion over the past few decades. However, this expansion has been matched by growing concerns over its environmental impacts. This article utilizes comparative legal analysis to explore the legal systems of governance for the environmental performance of marine aquaculture in four case study countries. Two are members of the European Community (Scotland, as part of the United Kingdom, and Greece), one is a recent accession country (Slovenia), and the fourth is closely linked to the European Community albeit geographically and legally disparate (Israel). 相似文献
68.
The sea otter (Enhydra lutris) is a popular exhibit animal in many zoos and aquariums worldwide. Captive sea otters from these populations are owned by the United States Fish and Wildlife Service (USFWS). The USFWS has requested that these sea otters be prevented from breeding in order to save captive space for wild rescued animals. Sea otters are often housed in mixed sex groups, therefore a chemical contraceptive method or surgical removal of gonads must be used to prevent potential pregnancy. The contraceptive, Suprelorin® or deslorelin, has been used in many different species to effectively suppress reproduction but duration of effect may vary not only between species but also individuals. Here, we report the effects of one to several consecutive deslorelin implants on gonadal reproductive hormones found in fecal samples from six captive sea otters (two males and four females) compared to two control otters (one male and one female) housed at three zoological institutions. We documented the longitudinal hormone signatures of many stages of the contraceptive cycle including pretreatment (PT), stimulatory phase (S), effective contraception (EC), and hormone reversal (HR) that was characterized by a return to normal hormone levels. Deslorelin was found to be an effective contraceptive in sea otters and was found to be reversible documented by a live birth following treatment, however the duration of suppression in females was much longer than expected with a 6‐month and a 1‐year implant lasting between 3 and 4 years in females. Zoo Biol. 32:307–315, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
69.
70.
Stephen E. Gerrard Alyssa M. Larson Alexander M. Klibanov Nigel K.H. Slater Carl V. Hanson Barbara F. Abrams Mary K. Morris 《Biotechnology and bioengineering》2013,110(7):2058-2062
The infectivity of high‐titer, cell‐free HIV in culture media and human milk is rapidly reduced upon exposure to polyethylene slides painted with the linear hydrophobic polycation N,N‐dodecyl,methyl‐polyethylenimine (DMPEI). Accompanying viral p24 protein and free viral RNA analysis of solutions exposed to DMPEI‐coated surfaces suggests that virion attachment to the polycationic surface and its subsequent inactivation are the likely mechanism of this phenomenon. Biotechnol. Bioeng. 2013; 110: 2058–2062. © 2013 Wiley Periodicals, Inc. 相似文献