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181.
N-Glycosylation has long been linked to protein folding and quality control in the endoplasmic reticulum (ER). Recent work has shown that O-linked glycosylation and the corresponding glycosyltransferases also participate in this important function. Notably, Protein O-fucosyltransferase 1 (Ofut1/Pofut1), a soluble, ER localized enzyme that fucosylates Epidermal Growth Factor-like (EGF) repeats, functions as a chaperone involved in the proper localization of the Notch receptor in certain contexts. Pofut2, a related enzyme that modifies Thrombospondin type I repeats (TSRs), has also been hypothesized to play a role in the folding and quality control of TSR-containing proteins. Both enzymes only modify fully folded substrates suggesting that they are able to distinguish between folded and unfolded structures. Pofuts have known physiological relevance and are conserved across metazoans. Though consensus sequences for O-fucosylation have been established and structures of both Pofuts have been studied, the mechanism of how they participate in protein folding is not known. This article discusses past and recent advances made in novel roles for these protein O-glycosyltransferases. 相似文献
182.
V. J. Rejish Kumar Cini Achuthan N. J. Manju Rosamma Philip I. S. Bright Singh 《Journal of industrial microbiology & biotechnology》2009,36(3):355-365
A packed bed bioreactor (PBBR) was developed for rapid establishment of nitrification in brackish water hatchery systems in
the tropics. The reactors were activated by immobilizing ammonia-oxidizing (AMONPCU-1) and nitrite-oxidizing (NIONPCU-1) bacterial
consortia on polystyrene and low-density polyethylene beads, respectively. Fluorescence in situ hybridization demonstrated
the presence of autotrophic nitrifiers belong to Nitrosococcus mobilis, lineage of β ammonia oxidizers and nitrite oxidizer Nitrobacter sp. in the consortia. The activated reactors upon integration to the hatchery system resulted in significant ammonia removal
(P < 0.01) culminating to its undetectable levels. Consequently, a significantly higher percent survival of larvae was observed
in the larval production systems. With spent water the reactors could establish nitrification with high percentage removal
of ammonia (78%), nitrite (79%) and BOD (56%) within 7 days of initiation of the process. PBBR is configured in such a way
to minimize the energy requirements for continuous operation by limiting the energy inputs to a single stage pumping of water
and aeration to the aeration cells. The PBBR shall enable hatchery systems to operate under closed recirculating mode and
pave the way for better water management in the aquaculture industry. 相似文献
183.
High-level expression of DNA architectural factor HMGA2 and its association with nucleosomes in human embryonic stem cells 总被引:2,自引:0,他引:2
The state of chromatin in human embryonic stem (hES) cells is a key factor determining stem cell identity. The non-histone chromatin-associated factor HMGA2 has been studied mostly in the mouse where its function seems critical for embryonic cell growth and adipocytic cell differentiation. Here we show that HMGA2 is highly expressed in two undifferentiated human embryonic stem cell lines at a level of at least 10(5) copies per individual stem cell. Interestingly, expression is further upregulated by a factor of three at day 7 of embryoid body formation, before it quickly drops to or below the level found in undifferentiated cells. We also show that HMGA2 is stably associated with inter- and metaphase hES cell chromatin, and that up to 12 HMGA2 protomers stably associate in vitro with a single nucleosome core particle of known atomic structure. Our data lend support to the possibility that HMGA2 interacts with nucleosomes in a way that imposes a global effect on the state of ES cell chromatin, which may contribute to the establishment of both ES cell identity and the initiation of specific differentiation programs. 相似文献
184.
Manes GA Masendycz P Nguyen T Achuthan A Dinh H Hamilton JA Scholz GM 《The FEBS journal》2006,273(8):1791-1804
The development of macrophages from myeloid progenitor cells is primarily controlled by the growth factor colony stimulating factor-1 (CSF-1) and its cognate receptor, a transmembrane tyrosine kinase encoded by the c-Fms proto-oncogene. The CSF-1 receptor exerts its biological effects on cells via a range of signaling proteins including Erk1/2 and Akt. Here we have investigated the potential involvement of the Src-like adapter protein (SLAP-2) in signaling by the CSF-1 receptor in mouse bone marrow-derived macrophages. RT-PCR analysis revealed constitutive expression of the SLAP-2 gene in bone marrow macrophages. Surprisingly, co-immunoprecipitation and GST binding experiments demonstrated that the CSF-1 receptor could bind to SLAP-2 in a ligand-independent manner. Furthermore, the binding of SLAP-2 to the CSF-1 receptor involved multiple domains of SLAP-2. SLAP-2 also bound c-Cbl, with the interaction being mediated, at least in part, by the unique C-terminal domain of SLAP-2. Overexpression of SLAP-2 in bone marrow macrophages partially suppressed the CSF-1-induced tyrosine phosphorylation and/or expression level of a approximately 80 kDa protein without affecting CSF-1-induced global tyrosine phosphorylation, or activation of Akt or Erk1/2. Significantly, CSF-1 stimulation induced serine phosphorylation of SLAP-2. Pharmacologic inhibition of specific protein kinases revealed that CSF-1-induced phosphorylation of SLAP-2 was dependent on JNK activity. Taken together, our results suggest that SLAP-2 could potentially be involved in signaling by the CSF-1 receptor. 相似文献
185.
Vasudevan Chandrasekaran Chang Jun Lee Ping Lin Robert E. Duke Lee G. Pedersen 《Journal of molecular modeling》2009,15(8):897-911
Protein Z-dependent protease inhibitor (ZPI) and antithrombin III (AT3) are members of the serpin superfamily of protease
inhibitors that inhibit factor Xa (FXa) and other proteases in the coagulation pathway. While experimental structural information
is available for the interaction of AT3 with FXa, at present there is no structural data regarding the interaction of ZPI
with FXa, and the precise role of this interaction in the blood coagulation pathway is poorly understood. In an effort to
gain a structural understanding of this system, we have built a solvent equilibrated three-dimensional structural model of
the Michaelis complex of human ZPI/FXa using homology modeling, protein–protein docking and molecular dynamics simulation
methods. Preliminary analysis of interactions at the complex interface from our simulations suggests that the interactions
of the reactive center loop (RCL) and the exosite surface of ZPI with FXa are similar to those observed from X-ray crystal
structure-based simulations of AT3/FXa. However, detailed comparison of our modeled structure of ZPI/FXa with that of AT3/FXa
points to differences in interaction specificity at the reactive center and in the stability of the inhibitory complex, due
to the presence of a tyrosine residue at the P1 position in ZPI, instead of the P1 arginine residue in AT3. The modeled structure
also shows specific structural differences between AT3 and ZPI in the heparin-binding and flexible N-terminal tail regions.
Our structural model of ZPI/FXa is also compatible with available experimental information regarding the importance for the
inhibitory action of certain basic residues in FXa.
Figure Solvent equilibrated models for protein z-dependent protease inhibitor and its initial reactive complex with coagulation factor
Xa (show here) are developed.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
V.C. and C.J.L. contributed equally to this work. The solvent-equilibrated PDB structure of the ZPI/FXa will be made available
upon request.
Conflict of interest statement The authors state that they have no conflict of interest. 相似文献
186.
Dahai Luo Na Wei Danny N. Doan Prasad N. Paradkar Yuwen Chong Andrew D. Davidson Masayo Kotaka Julien Lescar Subhash G. Vasudevan 《The Journal of biological chemistry》2010,285(24):18817-18827
The dengue virus (DENV) NS3 protein is essential for viral polyprotein processing and RNA replication. It contains an N-terminal serine protease region (residues 1–168) joined to an RNA helicase (residues 180–618) by an 11-amino acid linker (169–179). The structure at 3.15 Å of the soluble NS3 protein from DENV4 covalently attached to 18 residues of the NS2B cofactor region (NS2B18NS3) revealed an elongated molecule with the protease domain abutting subdomains I and II of the helicase (Luo, D., Xu, T., Hunke, C., Grüber, G., Vasudevan, S. G., and Lescar, J. (2008) J. Virol. 82, 173–183). Unexpectedly, using similar crystal growth conditions, we observed an alternative conformation where the protease domain has rotated by ∼161° with respect to the helicase domain. We report this new crystal structure bound to ADP-Mn2+ refined to a resolution of 2.2 Å. The biological significance for interdomain flexibility conferred by the linker region was probed by either inserting a Gly residue between Glu173 and Pro174 or replacing Pro174 with a Gly residue. Both mutations resulted in significantly lower ATPase and helicase activities. We next increased flexibility in the linker by introducing a Pro176 to Gly mutation in a DENV2 replicon system. A 70% reduction in luciferase reporter signal and a similar reduction in the level of viral RNA synthesis were observed. Our results indicate that the linker region has evolved to an optimum length to confer flexibility to the NS3 protein that is required both for polyprotein processing and RNA replication. 相似文献
187.
Stoyanka V. Krastanova Vasudevan Balaji Michele R. Holden Mary Sekiya Baodi Xue Esengul A. Momol Thomas J. Burr 《Transgenic research》2010,19(6):949-958
A truncated form of the Ti-plasmid virE2 gene from Agrobacterium tumefaciens strains C58 and A6, and A. vitis strain CG450 was transferred and expressed in somatic embryos of grapevine rootstocks 110 Richter (Vitis rupestris × V. berlandieri), 3309 Couderc (V. rupestris × V. riparia) and Teleki 5C (V. berlandieri × V. riparia) via Agrobacterium-mediated transformation to confer resistance to crown gall disease. Transformation was confirmed in 98% of the 322 lines
by enzyme-linked immunosorbent assay for the neomycin phosphotransferase II protein and 97% of 295 lines by polymerase chain
reaction for the truncated virE2 transgene. Southern blot analysis revealed the insertion of truncated virE2 at one to three loci in a subset of seven transgenic 110 Richter lines. In vitro resistance screening assays based on inoculations
of shoot internode sections showed reduced tumorigenicity and very small galls in 23 of 154 transgenic lines. Non-transformed
controls had a 100% tumorigenicity rate with very large galls. Disease resistance assay at the whole plant level in the greenhouse
revealed seven transgenic lines (3 lines of 110 Richter, 2 lines of 3309 Couderc and 2 lines of Teleki 5C) were resistant
to A. tumefaciens strain C58 and A. vitis strains TM4 and CG450 with a substantially reduced percentage of inoculation sites showing gall as compared to controls.
No association was found between the level of resistance to crown gall disease and the source Agrobacterium strain of virE2. Taken together, our data showed that resistance to crown gall disease can be achieved by expressing a truncated form of
virE2 in grapevines. 相似文献
188.
Anja B. Scheiff Swapnil G. Yerande Ali El-Tayeb Wenjin Li Gajanan S. Inamdar Kamala K. Vasu Vasudevan Sudarsanam Christa E. Müller 《Bioorganic & medicinal chemistry》2010,18(6):2195-2203
A series of 2-amino-5-benzoyl-4-phenylthiazole derivatives was investigated in radioligand binding studies at adenosine receptor (AdoR) subtypes with the goal to obtain potent and A1-selective antagonists. Acylation of the 2-amino group was found to be crucial for high A1 affinity. The best compound of the present series was 2-benzoylamino-5-p-methylbenzoyl-4-phenylthiazole (16m) showing a Ki value of 4.83 nM at rat and 57.4 nM at human A1 receptors combined with high selectivity versus the other AdoR subtypes. The compound behaved as an antagonist in GTP shift assays at A1 receptors. Compound 16m may serve as a new lead structure for the development of second-generation non-xanthine-derived A1 antagonists which have potential as novel drugs. 相似文献
189.
190.
Varghese Rosemol Neeravi Ayyanraj Jacob Jobin John Vasudevan Karthick Kumar Jones Lionel Subramanian Nithya Veeraraghavan Balaji 《Molecular biology reports》2021,48(4):3265-3276
Molecular Biology Reports - The emergence of multi drug resistant clone CC320 serotype19F/19A and their capsular (cps) antigenic variants due to selective pressures such as vaccine had been... 相似文献