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11.
The Escherichia coli chaperonin GroEL is a complex of identical subunit proteins (57 kDa each) arranged in a back-to-back stacking of two heptameric rings. Its hallmarks include nested positive intra-ring and negative inter-ring cooperativity in adenosine trisphosphate (ATP) binding and the ability to mediate the folding of newly transcribed and/or denatured substrate proteins. We performed unbiased molecular dynamics simulations of the GroEL subunit protein in explicit water both with and without the nucleotide KMgATP to understand better the details of the structural transitions that enable these behaviors. Placing KMgATP in the equatorial domain binding pocket of a t state subunit, which corresponds to a low ATP-affinity state, produced a short-lived (6 ns) state that spontaneously transitioned to the high ATP-affinity r state. The important feature of this transition is a large-scale rotation of the intermediate domain's helix M to close the ATP binding pocket. Pivoting of helix M is accompanied by counterclockwise rotation and slight deformation of the apical domain, important for lowering the affinity for substrate protein. Aligning simulation conformations into model heptamer rings demonstrates that the t-->r transition in one subunit is not sterically hindered by t state neighbors, but requires breakage of Arg(197)-Glu(386) intersubunit salt bridges, which are important for inter-ring positive cooperativity. Lowest-frequency quasi-harmonic modes of vibration computed pre- and post-transition clearly show that natural vibrations facilitate the transition. Finally, we propose a novel mechanism for inter-ring cooperativity in ATP binding inspired by the observation of spontaneous insertion of the side chain of Ala(480) into the empty nucleotide pocket. 相似文献
12.
Kapustin A Stepanova V Aniol N Cines DB Poliakov A Yarovoi S Lebedeva T Wait R Ryzhakov G Parfyonova Y Gursky Y Yanagisawa H Minashkin M Beabealashvilli R Vorotnikov A Bobik A Tkachuk V 《The Biochemical journal》2012,443(2):491-503
uPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, and binding to the uPAR (uPA receptor; also known as CD87), integrins and LRP1 (low-density lipoprotein receptor-related protein 1) which activate intracellular signalling pathways. In the present paper we report that uPA-mediated cell migration requires an interaction with fibulin-5. uPA stimulates migration of wild-type MEFs (mouse embryonic fibroblasts) (Fbln5+/+ MEFs), but has no effect on fibulin-5-deficient (Fbln5-/-) MEFs. Migration of MEFs in response to uPA requires an interaction of fibulin-5 with integrins, as MEFs expressing a mutant fibulin-5 incapable of binding integrins (Fbln(RGE/RGE) MEFs) do not migrate in response to uPA. Moreover, a blocking anti-(human β1-integrin) antibody inhibited the migration of PASMCs (pulmonary arterial smooth muscle cells) in response to uPA. Binding of uPA to fibulin-5 generates plasmin, which excises the integrin-binding N-terminal cbEGF (Ca2+-binding epidermal growth factor)-like domain, leading to loss of β1-integrin binding. We suggest that uPA promotes cell migration by binding to fibulin-5, initiating its cleavage by plasmin, which leads to its dissociation from β1-integrin and thereby unblocks the capacity of integrin to facilitate cell motility. 相似文献
13.
Margolin W 《Current biology : CB》2001,11(10):R395-R398
Placement of the division site in Escherichia coli is determined in part by three Min proteins. Recent studies have shown that MinE, previously thought to form a static ring near the division site at the midcell position, actually joins MinC and MinD in their rapid oscillation between the cell poles. 相似文献
14.
The scientific approach toward ecological risk assessment (ERA) has advanced greatly during the 1990s. This growth has been accompanied by the development of ERA guidance by USEPA Headquarters, individual USEPA Regions, state environmental agencies, as well as international agencies. This compilation of ERA guidance and procedural documents identifies many of the existing ERA reference materials from the regulatory and/or governmental agency arena. In addition, this compilation provides annotations pertaining to the focus of each reviewed document, and compares/contrasts the approaches presented in the documents. As such, the evaluation provides insight into some of the qualities and levels of detail provided by each document. Examples of documents which are highlighted include recently published USEPA's “Guidelines for Ecological Risk Assessment;” USEPA's “Ecological Risk Assessment Guidance for Superfund;” the U.S. Army's “Procedural Guidelines for Ecological Risk Assessments;” and Environment Canada's “Ecological Risk Assessments Under the Canadian Environmental Protection Act.” 相似文献
15.
Locations of the opp and supX genes of Salmonella typhimurium and Escherichia coli. 总被引:8,自引:10,他引:8 下载免费PDF全文
The chromosomal locations of the supX and opp loci of Salmonella typhimurium LT2 and Escherichia coli K-12 were identified and found to result in the same gene sequence in both species, namely, pyrF-cysB-supX-trpPOLEDCBA-tonB(chr)-opp. These results differ from a previously reported location of the opp gene on the E. coli chromosome. Evidence indicates that the opp gene lies between chr(tonB) and galU in S. typhimurium. 相似文献
16.
Emmanuel Margolin Youngjun J. Oh Matthew Verbeek Jason Naude Daniel Ponndorf Yulia Alexandrovna Meshcheriakova Hadrien Peyret Michiel T. van Diepen Ros Chapman Ann E. Meyers George Peter Lomonossoff Nobuyuki Matoba Anna‐Lise Williamson Edward P. Rybicki 《Plant biotechnology journal》2020,18(10):2109-2117
17.
Víctor M. Hernández-Rocamora Concepción García-Monta?és Belén Reija Bego?a Monterroso William Margolin Carlos Alfonso Silvia Zorrilla Germán Rivas 《The Journal of biological chemistry》2013,288(34):24625-24635
The interaction of MinC with FtsZ and its effects on FtsZ polymerization were studied under close to physiological conditions by a combination of biophysical methods. The Min system is a widely conserved mechanism in bacteria that ensures the correct placement of the division machinery at midcell. MinC is the component of this system that effectively interacts with FtsZ and inhibits the formation of the Z-ring. Here we report that MinC produces a concentration-dependent reduction in the size of GTP-induced FtsZ protofilaments (FtsZ-GTP) as demonstrated by analytical ultracentrifugation, dynamic light scattering, fluorescence correlation spectroscopy, and electron microscopy. Our experiments show that, despite being shorter, FtsZ protofilaments maintain their narrow distribution in size in the presence of MinC. The protein had the same effect regardless of its addition prior to or after FtsZ polymerization. Fluorescence anisotropy measurements indicated that MinC bound to FtsZ-GDP with a moderate affinity (apparent KD ∼10 μm at 100 mm KCl and pH 7.5) very close to the MinC concentration corresponding to the midpoint of the inhibition of FtsZ assembly. Only marginal binding of MinC to FtsZ-GTP protofilaments was observed by analytical ultracentrifugation and fluorescence correlation spectroscopy. Remarkably, MinC effects on FtsZ-GTP protofilaments and binding affinity to FtsZ-GDP were strongly dependent on ionic strength, being severely reduced at 500 mm KCl compared with 100 mm KCl. Our results support a mechanism in which MinC interacts with FtsZ-GDP, resulting in smaller protofilaments of defined size and having the same effect on both preassembled and growing FtsZ protofilaments. 相似文献
18.
Kung Ban Sandra Duffy Yelena Khakham Vicky M. Avery Andrew Hughes Oliver Montagnat Kasiram Katneni Eileen Ryan Jonathan B. Baell 《Bioorganic & medicinal chemistry letters》2010,20(20):6024-6029
We report on the discovery of 3-alkylthio-1,2,4-triazine dimers that are potently toxic to Plasmodium falciparum, with single digit nanomolar activity, and up to several thousand-fold lower toxicity to mammalian cells. They are equipotent against chloroquine-resistant strains of P. falciparum. 相似文献
19.
Genetic and functional analyses of the conserved C-terminal core domain of Escherichia coli FtsZ 下载免费PDF全文
In Escherichia coli, FtsZ is required for the recruitment of the essential cell division proteins FtsA and ZipA to the septal ring. Several C-terminal deletions of E. coli FtsZ, including one of only 12 amino acids that removes the highly conserved C-terminal core domain, failed to complement chromosomal ftsZ mutants when expressed on a plasmid. To identify key individual residues within the core domain, six highly conserved residues were replaced with alanines. All but one of these mutants (D373A) failed to complement an ftsZ chromosomal mutant. Immunoblot analysis demonstrated that whereas I374A and F377A proteins were unstable in the cell, L372A, D373A, P375A, and L378A proteins were synthesized at normal levels, suggesting that they were specifically defective in some aspect of FtsZ function. In addition, all four of the stable mutant proteins were able to localize and form rings at potential division sites in chromosomal ftsZ mutants, implying a defect in a function other than localization and multimerization. Because another proposed function of FtsZ is the recruitment of FtsA and ZipA, we tested whether the C-terminal core domain was important for interactions with these proteins. Using two different in vivo assays, we found that the 12-amino-acid truncation of FtsZ was defective in binding to FtsA. Furthermore, two point mutants in this region (L372A and P375A) showed weakened binding to FtsA. In contrast, ZipA was capable of binding to all four stable point mutants in the FtsZ C-terminal core but not to the 12-amino-acid deletion. 相似文献
20.