scholarly journals Solution structure of the MEF2A-DNA complex: structural basis for the modulation of DNA bending and specificity by MADS-box transcription factors

2000 ◽  
Vol 19 (11) ◽  
pp. 2615-2628 ◽  
Author(s):  
K. Huang
Keyword(s):  
Transcription Factors ◽  
Solution Structure ◽  
Dna Bending ◽  
Structural Basis ◽  
Mads Box ◽  
Complex Structural ◽  
Dna Complex

scholarly journals DNA binding by MADS-box transcription factors: a molecular mechanism for differential DNA bending.

1997 ◽  
Vol 17 (5) ◽  
pp. 2876-2887 ◽  
Author(s):  
A G West ◽  
P Shore ◽  
A D Sharrocks
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Serum Response Factor ◽  
Dna Bending ◽  
Binding Specificity ◽  
Single Amino Acid ◽  
Specific Gene ◽  
Mads Box ◽  
Dna Binding Specificity ◽  
Single Amino Acid Residue

The serum response factor (SRF) and myocyte enhancer factor 2A (MEF2A) represent two human members of the MADS-box transcription factor family. Each protein has a distinct biological function which is reflected by the distinct specificities of the proteins for coregulatory protein partners and DNA-binding sites. In this study, we have investigated the mechanism of DNA binding utilized by these two related transcription factors. Although SRF and MEF2A belong to the same family and contain related DNA-binding domains, their DNA-binding mechanisms differ in several key aspects. In contrast to the dramatic DNA bending induced by SRF, MEF2A induces minimal DNA distortion. A combination of loss- and gain-of-function mutagenesis identified a single amino acid residue located at the N terminus of the recognition helices as the critical mediator of this differential DNA bending. This residue is also involved in determining DNA-binding specificity, thus indicating a link between DNA bending and DNA-binding specificity determination. Furthermore, different basic residues within the putative recognition alpha-helices are critical for DNA binding, and the role of the C-terminal extensions to the MADS box in dimerization between SRF and MEF2A also differs. These important differences in the molecular interactions of SRF and MEF2A are likely to contribute to their differing roles in the regulation of specific gene transcription.

scholarly journals The structural basis of African swine fever virus pA104R binding to DNA and its inhibition by stilbene derivatives

2020 ◽  
Vol 117 (20) ◽  
pp. 11000-11009 ◽  
Author(s):  
Ruili Liu ◽  
Yeping Sun ◽  
Yan Chai ◽  
Su Li ◽  
Shihua Li ◽  
...  
Keyword(s):  
Dna Binding ◽  
African Swine Fever Virus ◽  
Dna Bending ◽  
Complex Structure ◽  
African Swine Fever ◽  
Fever Virus ◽  
Structural Basis ◽  
Bending Angle ◽  
Stilbene Derivatives ◽  
Dna Complex

African swine fever virus (ASFV) is a highly contagious nucleocytoplasmic large DNA virus (NCLDV) that causes nearly 100% mortality in swine. The development of effective vaccines and drugs against this virus is urgently needed. pA104R, an ASFV-derived histone-like protein, shares sequence and functional similarity with bacterial HU/IHF family members and is essential for viral replication. Herein, we solved the crystal structures of pA104R in its apo state as well as in complex with DNA. Apo-pA104R forms a homodimer and folds into an architecture conserved in bacterial heat-unstable nucleoid proteins/integration host factors (HUs/IHFs). The pA104R-DNA complex structure, however, uncovers that pA104R has a DNA binding pattern distinct from its bacterial homologs, that is, the β-ribbon arms of pA104R stabilize DNA binding by contacting the major groove instead of the minor groove. Mutations of the basic residues at the base region of the β-strand DNA binding region (BDR), rather than those in the β-ribbon arms, completely abolished DNA binding, highlighting the major role of the BDR base in DNA binding. An overall DNA bending angle of 93.8° is observed in crystal packing of the pA104R-DNA complex structure, which is close to the DNA bending angle in the HU-DNA complex. Stilbene derivatives SD1 and SD4 were shown to disrupt the binding between pA104R and DNA and inhibit the replication of ASFV in primary porcine alveolar macrophages. Collectively, these results reveal the structural basis of pA104R binding to DNA highlighting the importance of the pA104R-DNA interaction in the ASFV replication cycle and provide inhibitor leads for ASFV chemotherapy.

scholarly journals The Solution Structure of the Human ETS1-DNA Complex Reveals a Novel Mode of Binding and True Side Chain Intercalation

Cell ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 358 ◽  
Author(s):  
Milton H Werner ◽  
G.Marius Clore ◽  
Constance L Fisher ◽  
Robert J Fisher ◽  
Loc Trinh ◽  
...  
Keyword(s):  
Solution Structure ◽  
Side Chain ◽  
Dna Complex

scholarly journals Structural Basis for the C-Terminal Domain of Mycobacterium tuberculosis Ribosome Maturation Factor RimM to Bind Ribosomal Protein S19

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 597
Author(s):  
Haoran Zhang ◽  
Qiuxiang Zhou ◽  
Chenyun Guo ◽  
Liubin Feng ◽  
Huilin Wang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ribosomal Protein ◽  
Solution Structure ◽  
Molecular Mechanisms ◽  
Structural Model ◽  
Ribosomal Subunit ◽  
Structural Basis ◽  
Hydrophobic Core ◽  
Terminal Domain ◽  
Ribosomal Protein S19

Multidrug-resistant tuberculosis (TB) is a serious threat to public health, calling for the development of new anti-TB drugs. Chaperon protein RimM, involved in the assembly of ribosomal protein S19 into 30S ribosomal subunit during ribosome maturation, is a potential drug target for TB treatment. The C-terminal domain (CTD) of RimM is primarily responsible for binding S19. However, both the CTD structure of RimM from Mycobacterium tuberculosis (MtbRimMCTD) and the molecular mechanisms underlying MtbRimMCTD binding S19 remain elusive. Here, we report the solution structure, dynamics features of MtbRimMCTD, and its interaction with S19. MtbRimMCTD has a rigid hydrophobic core comprised of a relatively conservative six-strand β-barrel, tailed with a short α-helix and interspersed with flexible loops. Using several biophysical techniques including surface plasmon resonance (SPR) affinity assays, nuclear magnetic resonance (NMR) assays, and molecular docking, we established a structural model of the MtbRimMCTD–S19 complex and indicated that the β4-β5 loop and two nonconserved key residues (D105 and H129) significantly contributed to the unique pattern of MtbRimMCTD binding S19, which might be implicated in a form of orthogonality for species-dependent RimM–S19 interaction. Our study provides the structural basis for MtbRimMCTD binding S19 and is beneficial to the further exploration of MtbRimM as a potential target for the development of new anti-TB drugs.

First X-ray Structure of aN-Naphthaloyl-Tethered Chiral Dirhodium(II) Complex: Structural Basis for Tether Substitution Improving Asymmetric Control in Olefin Cyclopropanation

2010 ◽  
Vol 16 (11) ◽  
pp. 3291-3295 ◽  
Author(s):  
Ashraf Ghanem ◽  
Michael G. Gardiner ◽  
Rachel M. Williamson ◽  
Paul Müller
Keyword(s):  
Structural Basis ◽  
X Ray ◽  
Complex Structural
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