uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 46) Show all publications
Cordeiro, Y., Vieira, T., Kovachev, P. S., Sanyal, S. & Silva, J. L. (2019). Modulation of p53 and prion protein aggregation by RNA. Biochimica et Biophysica Acta - Proteins and Proteomics, 1867(10), 933-940
Open this publication in new window or tab >>Modulation of p53 and prion protein aggregation by RNA
Show others...
2019 (English)In: Biochimica et Biophysica Acta - Proteins and Proteomics, ISSN 1570-9639, E-ISSN 1878-1454, Vol. 1867, no 10, p. 933-940Article, review/survey (Refereed) Published
Abstract [en]

Several RNA-binding proteins undergo reversible liquid-liquid phase transitions, which, in pathological conditions, might evolve into transitions to solid-state phases, giving rise to amyloid structures. Amyloidogenic and prion-like proteins, such as the tumor suppressor protein p53 and the mammalian prion protein (PrP), bind RNAs specifically or nonspecifically, resulting in changes in their propensity to undergo aggregation. Mutant p53 aggregation seems to play a crucial role in cancer through loss of function, negative dominance and gain of function. PrP conversion modulated by RNA results in highly toxic aggregates. Here, we review data on the modulatory action of RNAs on the aggregation of both proteins.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-393757 (URN)10.1016/j.bbapap.2019.02.006 (DOI)000480375700008 ()30826454 (PubMedID)
Available from: 2019-09-27 Created: 2019-09-27 Last updated: 2019-09-27Bibliographically approved
Holm, M., Mandava, C. S., Ehrenberg, M. & Sanyal, S. (2019). The mechanism of error induction by the antibiotic viomycin provides insight into the fidelity mechanism of translation. eLIFE, 8, Article ID e46124.
Open this publication in new window or tab >>The mechanism of error induction by the antibiotic viomycin provides insight into the fidelity mechanism of translation
2019 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 8, article id e46124Article in journal (Refereed) Published
Abstract [en]

Applying pre-steady state kinetics to an Escherichia-coli-based reconstituted translation system, we have studied how the antibiotic viomycin affects the accuracy of genetic code reading. We find that viomycin binds to translating ribosomes associated with a ternary complex (TC) consisting of elongation factor Tu (EF-Tu), aminoacyl tRNA and GTP, and locks the otherwise dynamically flipping monitoring bases A1492 and A1493 into their active conformation. This effectively prevents dissociation of near- and non-cognate TCs from the ribosome, thereby enhancing errors in initial selection. Moreover, viomycin shuts down proofreading-based error correction. Our results imply a mechanism in which the accuracy of initial selection is achieved by larger backward rate constants toward TC dissociation rather than by a smaller rate constant for GTP hydrolysis for near- and non-cognate TCs. Additionally, our results demonstrate that translocation inhibition, rather than error induction, is the major cause of cell growth inhibition by viomycin.

Place, publisher, year, edition, pages
ELIFE SCIENCES PUBLICATIONS LTD, 2019
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-390687 (URN)10.7554/eLife.46124 (DOI)000473013700001 ()31172942 (PubMedID)
Funder
Swedish Research Council, 2018-05498Swedish Research Council, 2016-06264Knut and Alice Wallenberg Foundation, KAW 2011.0081Knut and Alice Wallenberg Foundation, KAW 2017.0055Carl Tryggers foundation , CTS 18: 338Wenner-Gren Foundations, UPD2017-0238
Available from: 2019-08-14 Created: 2019-08-14 Last updated: 2019-08-14Bibliographically approved
Vovusha, H., Banerjee, D., Yadav, M. K., Perrozzi, F., Ottaviano, L., Sanyal, S. & Sanyal, B. (2018). Binding Characteristics of Anticancer Drug Doxorubicin with Two-Dimensional Graphene and Graphene Oxide: Insights from Density Functional Theory Calculations and Fluorescence Spectroscopy. The Journal of Physical Chemistry C, 122(36), 21031-21038
Open this publication in new window or tab >>Binding Characteristics of Anticancer Drug Doxorubicin with Two-Dimensional Graphene and Graphene Oxide: Insights from Density Functional Theory Calculations and Fluorescence Spectroscopy
Show others...
2018 (English)In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 122, no 36, p. 21031-21038Article in journal (Refereed) Published
Abstract [en]

There has been a perpetual interest in identifying suitable nano-carriers for drug delivery. In this regard, graphene-based two-dimensional materials have been proposed and demonstrated as drug carriers. In this paper, we have investigated the adsorption characteristics of a widely used anticancer drug, doxorubicin (DOX), on graphene (G) and graphene oxide (GO) by density functional theory calculations and fluorescence and X-ray photoelectron spectroscopies. From the calculated structural and electronic properties, we have concluded that G is a better binder of DOX compared to GO, which is also supported by our fluorescence measurements. The binding of DOX to G is mainly based on strong pi-pi stacking interactions. Consistent with this result, we also found that the sp(2) regions of GO interact with DOX stronger than the sp(3) regions attached with the functional groups; the binding is characterized by pi-pi and hydrogen-bonding interactions, respectively.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2018
National Category
Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-366741 (URN)10.1021/acs.jpcc.8b04496 (DOI)000444920900049 ()
Funder
Swedish Research Council, 2016-05366Swedish Research Council, 20144423Swedish Research Council, 2017-05447Knut and Alice Wallenberg Foundation, KAW 2017.0055
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2019-05-17Bibliographically approved
Mishra, A. K., Morgon, N. H., Sanyal, S., de Souza, A. R. & Biswas, S. (2018). Catalytic O- to N-Alkyl Migratory Rearrangement: Transition Metal-Free Direct and Tandem Routes to N-Alkylated Pyridones and Benzothiazolones. Advanced Synthesis and Catalysis, 360(20), 3930-3939
Open this publication in new window or tab >>Catalytic O- to N-Alkyl Migratory Rearrangement: Transition Metal-Free Direct and Tandem Routes to N-Alkylated Pyridones and Benzothiazolones
Show others...
2018 (English)In: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 360, no 20, p. 3930-3939Article in journal (Refereed) Published
Abstract [en]

The present study reports the synthesis of N-alkylated pyridones and benzothiazolones via O- to N-alkyl group migration under transition metal-free TfOH-catalyzed reaction conditions for the first time, to the best of our knowledge. Primary as well as secondary alkyl groups smoothly migrate under the present reaction conditions. Moreover, a minor modification of the protocol used in this study is found to be applicable for an entirely new tandem synthesis of 2-alkoxy-N-heterocycles from the simplest starting materials in a solvent-free reaction conditions. Density Functional Theory (DFT) calculation identifies the energy species associated with the rearrangement, whereas, mechanistic experiments explore the role of the catalyst as the alkyl group transfer mediator.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH, 2018
Keywords
Benzothiazolones, Metal-free, Pyridones, Rearrangement, Tandem, DFT
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-369093 (URN)10.1002/adsc.201800664 (DOI)000447633800012 ()
Available from: 2019-02-18 Created: 2019-02-18 Last updated: 2019-02-18Bibliographically approved
Ge, X., Mandava, C. S., Lind, C., Åqvist, J. & Sanyal, S. (2018). Complementary charge-based interaction between the ribosomal-stalk protein L7/12 and IF2 is the key to rapid subunit association. Proceedings of the National Academy of Sciences of the United States of America, 115(18), 4649-4654
Open this publication in new window or tab >>Complementary charge-based interaction between the ribosomal-stalk protein L7/12 and IF2 is the key to rapid subunit association
Show others...
2018 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 18, p. 4649-4654Article in journal (Refereed) Published
Abstract [en]

The interaction between the ribosomal-stalk protein L7/12 (L12) and initiation factor 2 (IF2) is essential for rapid subunit association, but the underlying mechanism is unknown. Here, we have characterized the L12–IF2 interaction on Escherichia coli ribosomes using site-directed mutagenesis, fast kinetics, and molecular dynamics (MD) simulations. Fifteen individual point mutations were introduced into the C-terminal domain of L12 (L12-CTD) at helices 4 and 5, which constitute the common interaction site for translational GTPases. In parallel, 15 point mutations were also introduced into IF2 between the G4 and G5 motifs, which we hypothesized as the potential L12 interaction sites. The L12 and IF2 mutants were tested in ribosomal subunit association assay in a stopped-flow instrument. Those amino acids that caused defective subunit association upon substitution were identified as the molecular determinants of L12–IF2 interaction. Further, MD simulations of IF2 docked onto the L12-CTD pinpointed the exact interacting partners—all of which were positively charged on L12 and negatively charged on IF2, connected by salt bridges. Lastly, we tested two pairs of charge-reversed mutants of L12 and IF2, which significantly restored the yield and the rate of formation of the 70S initiation complex. We conclude that complementary charge-based interaction between L12-CTD and IF2 is the key for fast subunit association. Considering the homology of the G domain, similar mechanisms may apply for L12 interactions with other translational GTPases.

Keywords
protein synthesis, ribosomal protein L7/12, protein-protein interaction, ribosome, translation initiation
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-350185 (URN)10.1073/pnas.1802001115 (DOI)000431119600050 ()29686090 (PubMedID)
Funder
Swedish Research Council, 2014-4423; 2016-06264Knut and Alice Wallenberg Foundation, 2011.0081VINNOVA, 2013-8778
Available from: 2018-05-07 Created: 2018-05-07 Last updated: 2018-07-13Bibliographically approved
Fislage, M., Zhang, J., Brown, Z. P., Mandava, C. S., Sanyal, S., Ehrenberg, M. & Frank, J. (2018). Cryo-EM shows stages of initial codon selection on the ribosome by aa-tRNA in ternary complex with GTP and the GTPase-deficient EF-Tu(H84A). Nucleic Acids Research, 46(11), 5861-5874
Open this publication in new window or tab >>Cryo-EM shows stages of initial codon selection on the ribosome by aa-tRNA in ternary complex with GTP and the GTPase-deficient EF-Tu(H84A)
Show others...
2018 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 46, no 11, p. 5861-5874Article in journal (Refereed) Published
Abstract [en]

The GTPase EF-Tu in ternary complex with GTP and aminoacyl-tRNA (aa-tRNA) promotes rapid and accurate delivery of cognate aa-tRNAs to the ribosomal A site. Here we used cryo-EM to study the molecular origins of the accuracy of ribosome-aided recognition of a cognate ternary complex and the accuracy-amplifying role of themonitoring bases A1492, A1493 and G530 of the 16S rRNA. We used the GTPase-deficient EF-Tu variant H84A with native GTP, rather than non-cleavable GTP analogues, to trap a near-cognate ternary complex in high-resolution ribosomal complexes of varying codon-recognition accuracy. We found that ribosome complexes trapped by GTPase-deficicent ternary complex due to the presence of EF-TuH84A or non-cleavable GTP analogues have very similar structures. We further discuss speed and accuracy of initial aa-tRNA selection in terms of conformational changes of aa-tRNA and stepwise activation of the monitoring bases at the decoding center of the ribosome.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-361119 (URN)10.1093/nar/gky346 (DOI)000438362400042 ()29733411 (PubMedID)
Funder
Swedish Research Council, 2013-8778Swedish Research Council, 2014-4423Swedish Research Council, 2016-06264Swedish Research Council, 2017-00230Knut and Alice Wallenberg Foundation, KAW 2011.0081NIH (National Institute of Health), R01 GM29169
Available from: 2018-09-20 Created: 2018-09-20 Last updated: 2018-09-20Bibliographically approved
Li, Z., Ge, X., Zhang, Y., Zheng, L., Sanyal, S. & Gao, N. (2018). Cryo-EM structure of Mycobacterium smegmatis ribosome reveals two unidentified ribosomal proteins close to the functional centers [Letter to the editor]. Protein & cell, 9(4), 384-388
Open this publication in new window or tab >>Cryo-EM structure of Mycobacterium smegmatis ribosome reveals two unidentified ribosomal proteins close to the functional centers
Show others...
2018 (English)In: Protein & cell, ISSN 1674-8018, Vol. 9, no 4, p. 384-388Article in journal, Letter (Other academic) Published
National Category
Microbiology Cell Biology
Identifiers
urn:nbn:se:uu:diva-344575 (URN)10.1007/s13238-017-0456-9 (DOI)000428849800007 ()28875450 (PubMedID)
Funder
Swedish Research Council, 2013-8778; 2014-4423; 2016-06264; 2008-6593Knut and Alice Wallenberg Foundation, KAW 2011.0081
Available from: 2018-03-06 Created: 2018-03-06 Last updated: 2018-08-10Bibliographically approved
Vieler, M. & Sanyal, S. (2018). p53 Isoforms and Their Implications in Cancer. Cancers, 10(9), Article ID 288.
Open this publication in new window or tab >>p53 Isoforms and Their Implications in Cancer
2018 (English)In: Cancers, ISSN 2072-6694, Vol. 10, no 9, article id 288Article, review/survey (Refereed) Published
Abstract [en]

In this review we focus on the major isoforms of the tumor-suppressor protein p53, dysfunction of which often leads to cancer. Mutations of the TP53 gene, particularly in the DNA binding domain, have been regarded as the main cause for p53 inactivation. However, recent reports demonstrating abundance of p53 isoforms, especially the N-terminally truncated ones, in the cancerous tissues suggest their involvement in carcinogenesis. These isoforms are Delta 40p53, Delta 133p53, and Delta 160p53 (the names indicate their respective N-terminal truncation). Due to the lack of structural and functional characterizations the modes of action of the p53 isoforms are still unclear. Owing to the deletions in the functional domains, these isoforms can either be defective in DNA binding or more susceptive to altered 'responsive elements' than p53. Furthermore, they may exert a 'dominant negative effect' or induce more aggressive cancer by the 'gain of function'. One possible mechanism of p53 inactivation can be through tetramerization with the Delta 133p53 and Delta 160p53 isoforms-both lacking part of the DNA binding domain. A recent report and unpublished data from our laboratory also suggest that these isoforms may inactivate p53 by fast aggregation-possibly due to ectopic overexpression. We further discuss the evolutionary significance of the p53 isoforms.

Place, publisher, year, edition, pages
MDPI, 2018
Keywords
p53, cancer, p53 isoform, Delta 133p53, Delta 160p53, Delta 40p53, aggregation, prion
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-370049 (URN)10.3390/cancers10090288 (DOI)000448139800012 ()30149602 (PubMedID)
Funder
Swedish Research Council, 2014-4423Swedish Research Council, 2016-06264Knut and Alice Wallenberg Foundation, KAW 2017.0055
Available from: 2018-12-20 Created: 2018-12-20 Last updated: 2018-12-20Bibliographically approved
Liljas, A. & Sanyal, S. (2018). The enigmatic ribosomal stalk. Quarterly reviews of biophysics (Print), 51, Article ID e12.
Open this publication in new window or tab >>The enigmatic ribosomal stalk
2018 (English)In: Quarterly reviews of biophysics (Print), ISSN 0033-5835, E-ISSN 1469-8994, Vol. 51, article id e12Article, review/survey (Refereed) Published
Abstract [en]

The large ribosomal subunit has a distinct feature, the stalk, extending outside the ribosome. In bacteria it is called the L12 stalk. The base of the stalk is protein uL10 to which two or three dimers of proteins bL12 bind. In archea and eukarya P1 and P2 proteins constitute the stalk. All these extending proteins, that have a high degree of flexibility due to a hinge between their N- and C-terminal parts, are essential for proper functionalization of some of the translation factors. The role of the stalk proteins has remained enigmatic for decades but is gradually approaching an understanding. In this review we summarise the knowhow about the structure and function of the ribosomal stalk till date starting from the early phase of ribosome research.

Place, publisher, year, edition, pages
Cambridge University Press, 2018
Keywords
Ribosomal stalk, bL12, P1/P2, translational GTPases (trGTPases)
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-374867 (URN)10.1017/S0033583518000100 (DOI)000455259600001 ()
Funder
Swedish Research Council, 2014-4423Swedish Research Council, 2016-06264Knut and Alice Wallenberg Foundation, KAW 2017.0055
Available from: 2019-01-31 Created: 2019-01-31 Last updated: 2019-01-31Bibliographically approved
Masuda, I., Igarashi, T., Sakaguchi, R., Nitharwal, R. G., Takase, R., Han, K. Y., . . . Hou, Y.-M. (2017). A genetically encoded fluorescent tRNA is active in live-cell protein synthesis. Nucleic Acids Research, 45(7), 4081-4093
Open this publication in new window or tab >>A genetically encoded fluorescent tRNA is active in live-cell protein synthesis
Show others...
2017 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 45, no 7, p. 4081-4093Article in journal (Refereed) Published
Abstract [en]

Transfer RNAs (tRNAs) perform essential tasks for all living cells. They are major components of the ribosomal machinery for protein synthesis and they also serve in non-ribosomal pathways for regulation and signaling metabolism. We describe the development of a genetically encoded fluorescent tRNA fusion with the potential for imaging in live Escherichia coli cells. This tRNA fusion carries a Spinach aptamer that becomes fluorescent upon binding of a cell-permeable and non-toxic fluorophore. We show that, despite having a structural framework significantly larger than any natural tRNA species, this fusion is a viable probe for monitoring tRNA stability in a cellular quality control mechanism that degrades structurally damaged tRNA. Importantly, this fusion is active in E. coli live-cell protein synthesis allowing peptidyl transfer at a rate sufficient to support cell growth, indicating that it is accommodated by translating ribosomes. Imaging analysis shows that this fusion and ribosomes are both excluded from the nucleoid, indicating that the fusion and ribosomes are in the cytosol together possibly engaged in protein synthesis. This fusion methodology has the potential for developing new tools for live-cell imaging of tRNA with the unique advantage of both stoichiometric labeling and broader application to all cells amenable to genetic engineering.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2017
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-321801 (URN)10.1093/nar/gkw1229 (DOI)000399448400047 ()27956502 (PubMedID)
Funder
NIH (National Institute of Health), GM112659 GM114343 GM108972
Note

The two first authors contributed equally to this work.

Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2017-05-11Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-7124-792X

Search in DiVA

Show all publications