scholarly journals Structural variation affecting DNA backbone interactions underlies adaptation of B3 DNA binding domains to constraints imposed by protein architecture

2020 ◽  
Author(s):  
Haiyan Jia ◽  
Masaharu Suzuki ◽  
Donald R. McCarty
Keyword(s):  
Dna Binding ◽  
Electrostatic Interactions ◽  
Structural Variation ◽  
General Mechanism ◽  
Sequence Specificity ◽  
In Planta ◽  
Dna Binding Domains ◽  
Cis Element ◽  
Binding Domains ◽  
Dna Backbone

ABSTRACTFunctional diversification of transcription factor families through variation in modular domain architectures has played a central role in the independent evolution of gene regulatory networks underlying complex development in plants and animals. Here we show that architecture has in turn constrained evolution of B3 DNA binding domains in the B3 network regulating embryo formation in plants. B3 domains of ABI3, FUS3, LEC2 and VAL1 proteins recognize the same cis-element. ABI3 and VAL1 have complex architectures that physically integrate cis-element recognition with other signals, whereas LEC2 and FUS3 have reduced architectures conducive to their roles as pioneer activators. Qualitatively different activities of LEC2 and ABI3 B3 domains measured in vivo and in vitro are attributed in part to clade-specific substitutions in three amino acids that interact with the DNA backbone. Activities of FUS3 and VAL1 B3 domains show a similar correlation with architectural complexity. Domain-swap analyses in planta show that in a complex architecture setting the attenuated activities of ABI3 and VAL1 B3 domains are required for proper integration of ciselement recognition with hormone signalling. These results highlight modes of structural variation affecting non-specific, electrostatic interactions with the DNA backbone as a general mechanism allowing adaptation of DNA binding affinity to architectural constraints while preserving DNA sequence specificity.

scholarly journals Slow, heterogeneous NFκB single molecule conformational dynamics and implications for function

2021 ◽  
Author(s):  
Wei Chen ◽  
Wei Liu ◽  
Peter Wolynes ◽  
Elizabeth A. Komives
Keyword(s):  
Dna Binding ◽  
Single Molecule ◽  
Electrostatic Interactions ◽  
Bound States ◽  
Conformational Dynamics ◽  
Dna Binding Domains ◽  
Single Molecule Fret ◽  
Binding Domains ◽  
Lower Amplitude ◽  
Slow Motions

The transcription factor NFκB (RelA-p50) is a multidomain protein that binds DNA and its inhibitor, IκBα with apparently different conformations. We used single-molecule FRET to characterize the interdomain motions of the N-terminal DNA-binding domains in the free protein and also in various bound states. Several surprising results emerged from this study. First, the domains moved with respect to each other on several widely different timescales from hundreds of milliseconds to minutes. The free NFκB displayed stochastic motions leading to a broad distribution of states, ranging from very low-FRET states to high-FRET states. Varying the ionic strength altered the slow motions suggesting that they may be due to different weak electrostatic interactions between the domains creating a rugged energy landscape. Third, the DNA-binding domains continued to be mobile even when the protein was bound to its cognate DNA, but in this case the majority of the states were either high-FRET, a state expected from the available x-ray structures, or low-FRET, a state consistent with one of the DNA-binding domains dissociated. The fluctuations of the DNA-bound states were of lower amplitude and slightly faster frequency. Fourth, the inhibitor, IκBα freezes the domains into a low-FRET state, expected to be incapable of binding DNA. Neutralization of five acidic residues in the IκBα PEST sequence, which was previously shown to impair IκBαs ability to strip NFκB from the DNA, also impaired its ability to freeze the domains into a low-FRET state indicating that the freezing of motions of the DNA-binding domains is essential for efficient molecular stripping.

scholarly journals Diverse Eukaryotic CGG-Binding Proteins Produced by Independent Domestications of hAT Transposons

2021 ◽  
Author(s):  
Isaac Yellan ◽  
Ally W H Yang ◽  
Timothy R Hughes
Keyword(s):  
Dna Binding ◽  
Binding Proteins ◽  
Sequence Specificity ◽  
Binding Motifs ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Dna Binding Motifs ◽  
Wide Range ◽  
Human Transcription Factor ◽  
Hat Transposons

Abstract The human transcription factor (TF) CGGBP1 (CGG-binding protein) is conserved only in amniotes and is believed to derive from the zf-BED and Hermes transposase DNA-binding domains (DBDs) of a hAT DNA transposon. Here, we show that sequence-specific DNA-binding proteins with this bipartite domain structure have resulted from dozens of independent hAT domestications in different eukaryotic lineages. CGGBPs display a wide range of sequence specificity, usually including preferences for CGG or CGC trinucleotides, whereas some bind AT-rich motifs. The CGGBPs are almost entirely nonsyntenic, and their protein sequences, DNA-binding motifs, and patterns of presence or absence in genomes are uncharacteristic of ancestry via speciation. At least eight CGGBPs in the coelacanth Latimeria chalumnae bind distinct motifs, and the expression of the corresponding genes varies considerably across tissues, suggesting tissue-restricted function.

scholarly journals Mechanistic Heterogeneity in Site Recognition by the Structurally Homologous DNA-binding Domains of the ETS Family Transcription Factors Ets-1 and PU.1

2014 ◽  
Vol 289 (31) ◽  
pp. 21605-21616 ◽  
Author(s):  
Shuo Wang ◽  
Miles H. Linde ◽  
Manoj Munde ◽  
Victor D. Carvalho ◽  
W. David Wilson ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Ets Family ◽  
Site Recognition

scholarly journals Protein Kinase A Signaling Pathway Regulates Transcriptional Activity of SAF-1 by Unmasking Its DNA-binding Domains

2003 ◽  
Vol 278 (25) ◽  
pp. 22586-22595 ◽  
Author(s):  
Alpana Ray ◽  
Papiya Ray ◽  
Nicole Guthrie ◽  
Arvind Shakya ◽  
Deepak Kumar ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Dna Binding ◽  
Protein Kinase A ◽  
Signaling Pathway ◽  
Transcriptional Activity ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Kinase A

scholarly journals Role of Papillomavirus E1 Initiator Dimerization in DNA Replication

2005 ◽  
Vol 79 (13) ◽  
pp. 8661-8664 ◽  
Author(s):  
Stephen Schuck ◽  
Arne Stenlund
Keyword(s):  
Dna Replication ◽  
Dna Binding ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Severe Effect ◽  
Origin Of Dna Replication ◽  
Initiation Of Dna Replication

ABSTRACT Viral initiator proteins are polypeptides that form oligomeric complexes on the origin of DNA replication (ori). These complexes carry out a multitude of functions related to initiation of DNA replication, and although many of these functions have been characterized biochemically, little is understood about how the complexes are assembled. Here we demonstrate that loss of one particular interaction, the dimerization between E1 DNA binding domains, has a severe effect on DNA replication in vivo but has surprisingly modest effects on most individual biochemical activities in vitro. We conclude that the dimer interaction is primarily required for initial recognition of ori.

scholarly journals Cdc13 N-Terminal Dimerization, DNA Binding, and Telomere Length Regulation

2010 ◽  
Vol 30 (22) ◽  
pp. 5325-5334 ◽  
Author(s):  
Meghan T. Mitchell ◽  
Jasmine S. Smith ◽  
Mark Mason ◽  
Sandy Harper ◽  
David W. Speicher ◽  
...  
Keyword(s):  
Dna Binding ◽  
Telomere Length ◽  
Functional Characterization ◽  
Point Mutations ◽  
Telomeric Dna ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Length Regulation ◽  
Telomere Length Regulation

ABSTRACT The essential yeast protein Cdc13 facilitates chromosome end replication by recruiting telomerase to telomeres, and together with its interacting partners Stn1 and Ten1, it protects chromosome ends from nucleolytic attack, thus contributing to genome integrity. Although Cdc13 has been studied extensively, the precise role of its N-terminal domain (Cdc13N) in telomere length regulation remains unclear. Here we present a structural, biochemical, and functional characterization of Cdc13N. The structure reveals that this domain comprises an oligonucleotide/oligosaccharide binding (OB) fold and is involved in Cdc13 dimerization. Biochemical data show that Cdc13N weakly binds long, single-stranded, telomeric DNA in a fashion that is directly dependent on domain oligomerization. When introduced into full-length Cdc13 in vivo, point mutations that prevented Cdc13N dimerization or DNA binding caused telomere shortening or lengthening, respectively. The multiple DNA binding domains and dimeric nature of Cdc13 offer unique insights into how it coordinates the recruitment and regulation of telomerase access to the telomeres.

Conformational changes in the DNA-binding domains of the ecdysteroid receptor during the formation of a complex with the hsp27 response element

2012 ◽  
Vol 30 (4) ◽  
pp. 379-393 ◽  
Author(s):  
Szymon Pakuła ◽  
Marek Orłowski ◽  
Grzegorz Rymarczyk ◽  
Tomasz Krusiński ◽  
Michał Jakób ◽  
...  
Keyword(s):  
Dna Binding ◽  
Conformational Changes ◽  
Response Element ◽  
Ecdysteroid Receptor ◽  
Dna Binding Domains ◽  
Binding Domains

scholarly journals Differential Gene Regulation by Selective Association of Transcriptional Coactivators and bZIP DNA-Binding Domains

2006 ◽  
Vol 26 (16) ◽  
pp. 5969-5982 ◽  
Author(s):  
Benoit Miotto ◽  
Kevin Struhl
Keyword(s):  
Dna Binding ◽  
Regulation Of Gene Expression ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Transcriptional Coactivators ◽  
Differential Gene Regulation ◽  
Arginine Residues ◽  
Contact Dna ◽  
Bzip Proteins ◽  
Basic Region

ABSTRACT bZIP DNA-binding domains are targets for viral and cellular proteins that function as transcriptional coactivators. Here, we show that MBF1 and the related Chameau and HBO1 histone acetylases interact with distinct subgroups of bZIP proteins, whereas pX does not discriminate. Selectivity of Chameau and MBF1 for bZIP proteins is mediated by residues in the basic region that lie on the opposite surface from residues that contact DNA. Chameau functions as a specific coactivator for the AP-1 class of bZIP proteins via two arginine residues. A conserved glutamic acid/glutamine in the linker region underlies MBF1 specificity for a subgroup of bZIP factors. Chameau and MBF1 cannot synergistically coactivate transcription due to competitive interactions with the basic region, but either protein can synergistically coactivate with pX. Analysis of Jun derivatives that selectively interact with these coactivators reveals that MBF1 is crucial for the response to oxidative stress, whereas Chameau is important for the response to chemical and osmotic stress. Thus, the bZIP domain mediates selective interactions with coactivators and hence differential regulation of gene expression.

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