scholarly journals Roles of conformational disorder and downhill folding in modulating protein–DNA recognition

2017 ◽  
Vol 19 (42) ◽  
pp. 28527-28539 ◽  
Author(s):  
Xiakun Chu ◽  
Victor Muñoz

Transcription factors search for their target DNA siteviaa mix of conventional 3D diffusion and 1D diffusion along the DNA molecule. We find that the presence of conformational disorder on the protein domain that binds DNA enables a gliding mode that results in accelerated 1D diffusion.

2017 ◽  
Vol 121 (13) ◽  
pp. 2748-2758 ◽  
Author(s):  
Suela Xhani ◽  
Shingo Esaki ◽  
Kenneth Huang ◽  
Noa Erlitzki ◽  
Gregory M. K. Poon

Author(s):  
Avinash S. Punekar ◽  
Jonathan Porter ◽  
Stephen B. Carr ◽  
Simon E. V. Phillips

MetR, a LysR-type transcriptional regulator (LTTR), has been extensively studied owing to its role in the control of methionine biosynthesis in proteobacteria. A MetR homodimer binds to a 24-base-pair operator region of themetgenes and specifically recognizes the interrupted palindromic sequence 5′-TGAA-N5-TTCA-3′. Mechanistic details underlying the interaction of MetR with its target DNA at the molecular level remain unknown. In this work, the crystal structure of the DNA-binding domain (DBD) of MetR was determined at 2.16 Å resolution. MetR-DBD adopts a winged-helix–turn–helix (wHTH) motif and shares significant fold similarity with the DBD of the LTTR protein BenM. Furthermore, a data-driven macromolecular-docking strategy was used to model the structure of MetR-DBD bound to DNA, which revealed that a bent conformation of DNA is required for the recognition helix α3 and the wing loop of the wHTH motif to interact with the major and minor grooves, respectively. Comparison of the MetR-DBD–DNA complex with the crystal structures of other LTTR-DBD–DNA complexes revealed residues that may confer operator-sequence binding specificity for MetR. Taken together, the results show that MetR-DBD uses a combination of direct base-specific interactions and indirect shape recognition of the promoter to regulate the transcription ofmetgenes.


Retrovirology ◽  
2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Erik Serrao ◽  
Allison Ballandras-Colas ◽  
Peter Cherepanov ◽  
Goedele N Maertens ◽  
Alan N Engelman
Keyword(s):  

2008 ◽  
Vol 5 (3) ◽  
pp. 303-312 ◽  
Author(s):  
Ilaria Lampronti ◽  
Mahmud T. H. Khan ◽  
Monica Borgatti ◽  
Nicoletta Bianchi ◽  
Roberto Gambari

Several transcription factors (TFs) play crucial roles in governing the expression of different genes involved in the immune response, embryo or cell lineage development, cell apoptosis, cell cycle progression, oncogenesis, repair and fibrosis processes and inflammation. As far as inflammation, TFs playing pivotal roles are nuclear factor kappa B (NF-kB), activator protein (AP-1), signal transducer and activator of transcription (STATs), cAMP response element binding protein (CREB) and GATA-1 factors. All these TFs regulate the expression of pro-inflammatory cytokines and are involved in the pathogenesis of a number of human disorders, particularly those with an inflammatory component. Since several medicinal plants can be employed to produce extracts exhibiting biological effects and because alteration of gene transcription represents a very interesting approach to control the expression of selected genes, this study sought to verify the ability of several extracts derived from Bangladeshi medicinal plants in interfering with molecular interactions between different TFs and specific DNA sequences. We first analyzed the antiproliferative activity of 19 medicinal plants on different human cell lines, including erythroleukemia K562, B lymphoid Raji and T lymphoid Jurkat cell lines. Secondly, we employed the electrophoretic mobility shift assay as a suitable technique for a fast screening of plant extracts altering the binding between NF-kB, AP-1, GATA-1, STAT-3, CREB and the relative target DNA elements.


Cell ◽  
2016 ◽  
Vol 167 (7) ◽  
pp. 1814-1828.e12 ◽  
Author(s):  
Hui Yang ◽  
Pu Gao ◽  
Kanagalaghatta R. Rajashankar ◽  
Dinshaw J. Patel
Keyword(s):  

2014 ◽  
Vol 10 (9) ◽  
pp. e1003804 ◽  
Author(s):  
Xiakun Chu ◽  
Fei Liu ◽  
Brian A. Maxwell ◽  
Yong Wang ◽  
Zucai Suo ◽  
...  

Genetics ◽  
1991 ◽  
Vol 128 (4) ◽  
pp. 687-694
Author(s):  
J Bender ◽  
J Kuo ◽  
N Kleckner

Abstract Tn10 and IS10 transpose by a nonreplicative mechanism in which the transposon is excised from the donor molecule and integrated into a target DNA site, leaving behind a break at the original donor site. The fate of this broken donor DNA molecule is not known. We describe here two experiments that address this issue. One experiment demonstrates that a polar IS10 element gives rise to polarity-relief revertants at less than 1% the frequency of transposition of the same element in the same culture. In a second experiment, transpositions of an IS10 element from one site in the bacterial genome to another are selected and the resulting isolates examined for alterations at the donor site; none of 1088 such isolates exhibited a detectable change at the donor locus. These results are compatible with two possible fates of the transposon donor molecule: degradation ("donor suicide"), or restoration of the original information at the donor site by a recombinational repair mechanism analogous to double-strand break repair. These results argue against the possibility that the donor molecule gap is simply resealed by intramolecular rejoining.


Sensors ◽  
2019 ◽  
Vol 19 (24) ◽  
pp. 5425
Author(s):  
Huiying Ma ◽  
Xuejing Chen ◽  
Bangrong Lu ◽  
Yanhong Ji

We proposed a coding and decoding method of suspension array (SA) based on micro-quartz pieces (MQPs) with different optical thicknesses. The capture probes (cDNA) were grafted onto the surfaces of MQPs and specifically recognized and combined with the partial sequence of the target DNA (tDNA) to form a MQP-cDNA-tDNA complex. Quantum dot-labeled signal probes were then used to specifically recognize and bind another portion of the tDNA in the complex to form a double-probe sandwich structure. This optical thickness-encoded SA can be decoded and detected by a dual-wavelength digital holographic phase fluorescence microscope system. We conducted a series of DNA molecule detection experiments by using this encoding method. Control experiments confirmed the specificity of optical thickness-encoded SA in DNA detection. The concentration gradient experiments then demonstrated the response of the MQPs based SA to analyte concentration. Finally, we used the encoding method to detect three types of DNA in a single sample and confirmed the feasibility of the proposed optical thickness-encoded SA in multiplexed DNA detection. The detection results are stable, and the detection exhibits high specificity and good repeatability.


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