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131.
In prokaryotes, DNA replication is initiated by the binding of DnaA to the oriC region of the chromosome to load the primosome machinery and start a new replication round. Several proteins control these events in Escherichia coli to ensure that replication is precisely timed during the cell cycle. Here, we report the crystal structure of HobA (HP1230) at 1.7 A, a recently discovered protein that specifically interacts with DnaA protein from Helicobacter pylori (HpDnaA). We found that the closest structural homologue of HobA is a sugar isomerase (SIS) domain containing protein, the phosphoheptose isomerase from Pseudomonas aeruginosa. Remarkably, SIS proteins share strong sequence homology with DiaA from E. coli; yet, HobA and DiaA share no sequence homology. Thus, by solving the structure of HobA, we unexpectedly discovered that HobA is a H. pylori structural homologue of DiaA. By comparing the structure of HobA to a homology model of DiaA, we identified conserved, surface-accessible residues that could be involved in protein-protein interaction. Finally, we show that HobA specifically interacts with the N-terminal part of HpDnaA. The structural homology between DiaA and HobA strongly supports their involvement in the replication process and these proteins could define a new structural family of replication regulators in bacteria. 相似文献
132.
Cho K Agrawal GK Shibato J Jung YH Kim YK Nahm BH Jwa NS Tamogami S Han O Kohda K Iwahashi H Rakwal R 《Journal of proteome research》2007,6(9):3581-3603
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An integrative approach combining ion mobility mass spectrometry,X-ray crystallography,and nuclear magnetic resonance spectroscopy to study the conformational dynamics of α1-antitrypsin upon ligand binding
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Mun Peak Nyon Tanya Prentice Jemma Day John Kirkpatrick Ganesh N Sivalingam Geraldine Levy Imran Haq James A Irving David A Lomas John Christodoulou Bibek Gooptu Konstantinos Thalassinos 《Protein science : a publication of the Protein Society》2015,24(8):1301-1312
Native mass spectrometry (MS) methods permit the study of multiple protein species within solution equilibria, whereas ion mobility (IM)-MS can report on conformational behavior of specific states. We used IM-MS to study a conformationally labile protein (α1-antitrypsin) that undergoes pathological polymerization in the context of point mutations. The folded, native state of the Z-variant remains highly polymerogenic in physiological conditions despite only minor thermodynamic destabilization relative to the wild-type variant. Various data implicate kinetic instability (conformational lability within a native state ensemble) as the basis of Z α1-antitrypsin polymerogenicity. We show the ability of IM-MS to track such disease-relevant conformational behavior in detail by studying the effects of peptide binding on α1-antitrypsin conformation and dynamics. IM-MS is, therefore, an ideal platform for the screening of compounds that result in therapeutically beneficial kinetic stabilization of native α1-antitrypsin. Our findings are confirmed with high-resolution X-ray crystallographic and nuclear magnetic resonance spectroscopic studies of the same event, which together dissect structural changes from dynamic effects caused by peptide binding at a residue-specific level. IM-MS methods, therefore, have great potential for further study of biologically relevant thermodynamic and kinetic instability of proteins and provide rapid and multidimensional characterization of ligand interactions of therapeutic interest.PDB Code(s): 4PYW 相似文献
138.
Co-expressed Cyclin D variants cooperate to regulate proliferation of germline nuclei in a syncytium
Gunasekaran Subramaniam Coen Campsteijn Eric M Thompson 《Cell cycle (Georgetown, Tex.)》2015,14(13):2129-2141
The role of the G1-phase Cyclin D-CDK 4/6 regulatory module in linking germline stem cell (GSC) proliferation to nutrition is evolutionarily variable. In invertebrate Drosophila and C. elegans GSC models, G1 is nearly absent and Cyclin E is expressed throughout the cell cycle, whereas vertebrate spermatogonial stem cells have a distinct G1 and Cyclin D1 plays an important role in GSC renewal. In the invertebrate, chordate, Oikopleura, where germline nuclei proliferate asynchronously in a syncytium, we show a distinct G1-phase in which 2 Cyclin D variants are co-expressed. Cyclin Dd, present in both somatic endocycling cells and the germline, localized to germline nuclei during G1 before declining at G1/S. Cyclin Db, restricted to the germline, remained cytoplasmic, co-localizing in foci with the Cyclin-dependent Kinase Inhibitor, CKIa. These foci showed a preferential spatial distribution adjacent to syncytial germline nuclei at G1/S. During nutrient-restricted growth arrest, upregulated CKIa accumulated in arrested somatic endoreduplicative nuclei but did not do so in germline nuclei. In the latter context, Cyclin Dd levels gradually decreased. In contrast, the Cyclin Dbβ splice variant, lacking the Rb-interaction domain and phosphodegron, was specifically upregulated and the number of cytoplasmic foci containing this variant increased. This upregulation was dependent on stress response MAPK p38 signaling. We conclude that under favorable conditions, Cyclin Dbβ-CDK6 sequesters CKIa in the cytoplasm to cooperate with Cyclin Dd-CDK6 in promoting germline nuclear proliferation. Under nutrient-restriction, this sequestration function is enhanced to permit continued, though reduced, cycling of the germline during somatic growth arrest. 相似文献
139.
A three dimensional (3D) gold (Au) nanodendrite network porous structure constructed by a simple electrochemical synthetic method has been presented, and its utility for sensitive electrochemical measurement was demonstrated in this study. The 3D nanodendrite network porous structure was constructed on a platinum surface through electrodeposition of Au under the presence of hydrogen bubbles generated from the same surface. Iodide, used as a co-reagent, played an important role in the construction of the nanodendrite network by preventing continual growth of Au into larger agglomerates as well as inhibiting coalescence of neighboring nanodendrites. An electrochemical sensor incorporating the structure was built and used to detect As(III) in ultra low concentration range. For the purpose of comparison, bare gold and gold nanoparticle-incorporated electrodes were also prepared. With the use of 3D nanodendrite network porous structure, a much more sensitive detection of As(III) was possible due to its large surface area. 相似文献