scholarly journals Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1

2020 ◽  
Vol 48 (8) ◽  
pp. 4562-4571 ◽  
Author(s):  
Anna Traczyk ◽  
Chong Wai Liew ◽  
David James Gill ◽  
Daniela Rhodes
Keyword(s):  
Dna Binding ◽  
Dna Recognition ◽  
Binding Domain ◽  
Telomere Maintenance ◽  
Structural Basis ◽  
Dna Binding Domain ◽  
Double Stranded Dna ◽  
G Quadruplex ◽  
Quadruplex Formation ◽  
Telomeric Protein

Abstract G-quadruplexes are four-stranded nucleic acid structures involved in multiple cellular pathways including DNA replication and telomere maintenance. Such structures are formed by G-rich DNA sequences typified by telomeric DNA repeats. Whilst there is evidence for proteins that bind and regulate G-quadruplex formation, the molecular basis for this remains poorly understood. The budding yeast telomeric protein Rap1, originally identified as a transcriptional regulator functioning by recognizing double-stranded DNA binding sites, was one of the first proteins to be discovered to also bind and promote G-quadruplex formation in vitro. Here, we present the 2.4 Å resolution crystal structure of the Rap1 DNA-binding domain in complex with a G-quadruplex. Our structure not only provides a detailed insight into the structural basis for G-quadruplex recognition by a protein, but also gives a mechanistic understanding of how the same DNA-binding domain adapts to specifically recognize different DNA structures. The key observation is the DNA-recognition helix functions in a bimodal manner: In double-stranded DNA recognition one helix face makes electrostatic interactions with the major groove of DNA, whereas in G-quadruplex recognition a different helix face is used to make primarily hydrophobic interactions with the planar face of a G-tetrad.

The DNA-binding domain of BenM reveals the structural basis for the recognition of a T-N11-A sequence motif by LysR-type transcriptional regulators

2013 ◽  
Vol 69 (10) ◽  
pp. 1995-2007 ◽  
Author(s):  
Amer M. Alanazi ◽  
Ellen L. Neidle ◽  
Cory Momany
Keyword(s):  
Amino Acids ◽  
Dna Binding ◽  
Dna Recognition ◽  
Transcriptional Regulators ◽  
Binding Domain ◽  
Structural Basis ◽  
Binding Motif ◽  
Sequence Motif ◽  
Dna Binding Domain ◽  
Half Site

LysR-type transcriptional regulators (LTTRs) play critical roles in metabolism and constitute the largest family of bacterial regulators. To understand protein–DNA interactions, atomic structures of the DNA-binding domain and linker-helix regions of a prototypical LTTR, BenM, were determined by X-ray crystallography. BenM structures with and without bound DNA reveal a set of highly conserved amino acids that interact directly with DNA bases. At the N-terminal end of the recognition helix (α3) of a winged-helix–turn–helix DNA-binding motif, several residues create hydrophobic pockets (Pro30, Pro31 and Ser33). These pockets interact with the methyl groups of two thymines in the DNA-recognition motif and its complementary strand, T-N11-A. This motif usually includes some dyad symmetry, as exemplified by a sequence that binds two subunits of a BenM tetramer (ATAC-N7-GTAT). Gln29 forms hydrogen bonds to adenine in the first position of the recognition half-site (ATAC). Another hydrophobic pocket defined by Ala28, Pro30 and Pro31 interacts with the methyl group of thymine, complementary to the base at the third position of the half-site. Arg34 interacts with the complementary base of the 3′ position. Arg53, in the wing, provides AT-tract recognition in the minor groove. For DNA recognition, LTTRs use highly conserved interactions between amino acids and nucleotide bases as well as numerous less-conserved secondary interactions.

Structural basis of the p53 DNA binding domain and PUMA complex

2021 ◽  
Vol 548 ◽  
pp. 39-46
Author(s):  
Chang Woo Han ◽  
Han Na Lee ◽  
Mi Suk Jeong ◽  
So Young Park ◽  
Se Bok Jang
Keyword(s):  
Dna Binding ◽  
Binding Domain ◽  
Structural Basis ◽  
Dna Binding Domain

Novel Interaction of the Z-DNA Binding Domain of Human ADAR1 with the Oncogenic c-Myc Promoter G-Quadruplex

2014 ◽  
Vol 426 (14) ◽  
pp. 2594-2604 ◽  
Author(s):  
Hyun-Jin Kang ◽  
Tuong Vy Thi Le ◽  
Kyungmin Kim ◽  
Jeonghwan Hur ◽  
Kyeong Kyu Kim ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
G Quadruplex ◽  
Z Dna

The cavity in the hydrophobic core of Myb DNA-binding domain is reserved for DNA recognition and trans-activation

1996 ◽  
Vol 3 (2) ◽  
pp. 178-187 ◽  
Author(s):  
Kazuhiro Ogata ◽  
Chie Kanei-Ishii ◽  
Motoko Sasaki ◽  
Hideki Hatanaka ◽  
Aritaka Nagadoi ◽  
...  
Keyword(s):  
Dna Binding ◽  
Dna Recognition ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Hydrophobic Core

scholarly journals Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR–RXR

2020 ◽  
Vol 48 (17) ◽  
pp. 9969-9985
Author(s):  
Judit Osz ◽  
Alastair G McEwen ◽  
Maxime Bourguet ◽  
Frédéric Przybilla ◽  
Carole Peluso-Iltis ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Dna Binding ◽  
Structural Dynamics ◽  
Binding Domain ◽  
Retinoic Acid Receptors ◽  
Structural Basis ◽  
Dna Binding Domain ◽  
Binding Modes ◽  
Dna Complexes ◽  
X Ray

Abstract Retinoic acid receptors (RARs) as a functional heterodimer with retinoid X receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in regulated genes. Among them, the non-canonical DR0 elements are bound by RXR–RAR with comparable affinities to DR5 elements but DR0 elements do not act transcriptionally as independent RAREs. In this work, we present structural insights for the recognition of DR5 and DR0 elements by RXR–RAR heterodimer using x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium exchange coupled to mass spectrometry. We solved the crystal structures of RXR–RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR–RXR DNA-binding domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, the two molecules bound non-cooperatively on DR0 on opposite sides of the DNA. In addition, our data unveil the structural organization and dynamics of the multi-domain RXR–RAR DNA complexes providing evidence for DNA-dependent allosteric communication between domains. Differential binding modes between DR0 and DR5 were observed leading to differences in conformation and structural dynamics of the multi-domain RXR–RAR DNA complexes. These results reveal that the topological organization of the RAR binding element confer regulatory information by modulating the overall topology and structural dynamics of the RXR–RAR heterodimers.

DNA recognition by nuclear receptors

2004 ◽  
Vol 40 ◽  
pp. 59-72 ◽  
Author(s):  
Frank Claessens ◽  
Daniel T Gewirth
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Nuclear Receptors ◽  
Dna Sequences ◽  
Dna Recognition ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Core Motif ◽  
Response Elements ◽  
Sequence Recognition

The nuclear receptors constitute a large family of ligand-inducible transcription factors. The control of many genetic pathways requires the assembly of these nuclear receptors in defined transcription-activating complexes within control regions of ligand-responsive genes. An essential step is the interaction of the receptors with specific DNA sequences, called hormone-response elements (HREs). These response elements position the receptors, and the complexes recruited by them, close to the genes of which transcription is affected. HREs are bipartite elements that are composed of two hexameric core half-site motifs. The identity of the response elements resides in three features: the nucleotide sequence of the two core motif half-sites, the number of base pairs separating them and the relative orientation of the motifs. The DNA-binding domains of nuclear receptors consist of two zinc-nucleated modules and a C-terminal extension. Residues in the first module determine the specificity of the DNA recognition, while residues in the second module are involved in dimerization. Indeed, nuclear receptors bind to their HREs as either homodimers or heterodimers. Depending on the type of receptor, the C-terminal extension plays a role in sequence recognition, dimerization, or both. The DNA-binding domain is furthermore involved in several other functions including nuclear localization, and interaction with transcription factors and co-activators. It is also the target of post-translational modifications. The DNA-binding domain therefore plays a central role, not only in the correct binding of the receptors to the target genes, but also in the control of other steps of the action mechanism of nuclear receptors.

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