scholarly journals Structural basis of molecular recognition of helical histone H3 tail by PHD finger domains

2017 ◽  
Vol 474 (10) ◽  
pp. 1633-1651 ◽  
Author(s):  
Alessio Bortoluzzi ◽  
Anastasia Amato ◽  
Xavier Lucas ◽  
Manuel Blank ◽  
Alessio Ciulli
Keyword(s):  
Secondary Structure ◽  
Molecular Recognition ◽  
Histone H3 ◽  
Structural Basis ◽  
Bioinformatics Analyses ◽  
Histone Tails ◽  
Interacting Protein ◽  
Post Translational Modifications ◽  
Phd Finger ◽  
Additional Layer

The plant homeodomain (PHD) fingers are among the largest family of epigenetic domains, first characterized as readers of methylated H3K4. Readout of histone post-translational modifications by PHDs has been the subject of intense investigation; however, less is known about the recognition of secondary structure features within the histone tail itself. We solved the crystal structure of the PHD finger of the bromodomain adjacent to zinc finger 2A [BAZ2A, also known as TIP5 (TTF-I/interacting protein 5)] in complex with unmodified N-terminal histone H3 tail. The peptide is bound in a helical folded-back conformation after K4, induced by an acidic patch on the protein surface that prevents peptide binding in an extended conformation. Structural bioinformatics analyses identify a conserved Asp/Glu residue that we name ‘acidic wall’, found to be mutually exclusive with the conserved Trp for K4Me recognition. Neutralization or inversion of the charges at the acidic wall patch in BAZ2A, and homologous BAZ2B, weakened H3 binding. We identify simple mutations on H3 that strikingly enhance or reduce binding, as a result of their stabilization or destabilization of H3 helicity. Our work unravels the structural basis for binding of the helical H3 tail by PHD fingers and suggests that molecular recognition of secondary structure motifs within histone tails could represent an additional layer of regulation in epigenetic processes.

scholarly journals The conformation of the histone H3 tail inhibits association of the BPTF PHD finger with the nucleosome

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Emma A Morrison ◽  
Samuel Bowerman ◽  
Kelli L Sylvers ◽  
Jeff Wereszczynski ◽  
Catherine A Musselman
Keyword(s):  
Histone H3 ◽  
Md Simulations ◽  
Peptide Fragments ◽  
Histone Tails ◽  
Post Translational Modifications ◽  
Effector Domain ◽  
Phd Finger ◽  
Effector Domains ◽  
Chromatin Regulators ◽  
Nucleosomal Dna

Histone tails harbor a plethora of post-translational modifications that direct the function of chromatin regulators, which recognize them through effector domains. Effector domain/histone interactions have been broadly studied, but largely using peptide fragments of histone tails. Here, we extend these studies into the nucleosome context and find that the conformation adopted by the histone H3 tails is inhibitory to BPTF PHD finger binding. Using NMR spectroscopy and MD simulations, we show that the H3 tails interact robustly but dynamically with nucleosomal DNA, substantially reducing PHD finger association. Altering the electrostatics of the H3 tail via modification or mutation increases accessibility to the PHD finger, indicating that PTM crosstalk can regulate effector domain binding by altering nucleosome conformation. Together, our results demonstrate that the nucleosome context has a dramatic impact on signaling events at the histone tails, and highlights the importance of studying histone binding in the context of the nucleosome.

scholarly journals Structural basis for site-specific reading of unmodified R2 of histone H3 tail by UHRF1 PHD finger

Cell Research ◽  
2011 ◽  
Vol 21 (9) ◽  
pp. 1379-1382 ◽  
Author(s):  
Chengkun Wang ◽  
Jie Shen ◽  
Zhongzheng Yang ◽  
Ping Chen ◽  
Bin Zhao ◽  
...  
Keyword(s):  
Histone H3 ◽  
Structural Basis ◽  
Site Specific ◽  
Phd Finger ◽  
Specific Reading

scholarly journals Phosphorylation of Histone H3 Thr-45 Is Linked to Apoptosis

2009 ◽  
Vol 284 (24) ◽  
pp. 16575-16583 ◽  
Author(s):  
Paul J. Hurd ◽  
Andrew J. Bannister ◽  
Karen Halls ◽  
Mark A. Dawson ◽  
Michiel Vermeulen ◽  
...  
Keyword(s):  
Histone H3 ◽  
Histone Tails ◽  
Post Translational Modifications ◽  
Nucleosome Structure ◽  
Cytokine Inhibition ◽  
Dna Nicking ◽  
A Site ◽  
Histone Core

Numerous post-translational modifications have been identified in histones. Most of these occur within the histone tails, but a few have been identified within the histone core sequences. Histone core post-translational modifications have the potential to directly modulate nucleosome structure and consequently DNA accessibility. Here, we identify threonine 45 of histone H3 (H3T45) as a site of phosphorylation in vivo. We find that phosphorylation of H3T45 (H3T45ph) increases dramatically in apoptotic cells, around the time of DNA nicking. To further explore this connection, we analyzed human neutrophil cells because they are short-lived cells that undergo apoptosis in vivo. Freshly isolated neutrophils contain very little H3T45ph, whereas cells cultured for 20 h possess significant amounts; the kinetics of H3T45ph induction closely parallel those of caspase-3 activation. Cytokine inhibition of neutrophil apoptosis leads to reduced levels of H3T45ph. We identify protein kinase C-δ as the kinase responsible for H3T45ph in vitro and in vivo. Given the nucleosomal position of H3T45, we postulate that H3T45ph induces structural change within the nucleosome to facilitate DNA nicking and/or fragmentation.

scholarly journals Structural basis for molecular recognition and presentation of histone H3 By WDR5

2006 ◽  
Vol 25 (18) ◽  
pp. 4245-4252 ◽  
Author(s):  
Anja Schuetz ◽  
Abdellah Allali-Hassani ◽  
Fernando Martín ◽  
Peter Loppnau ◽  
Masoud Vedadi ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Histone H3 ◽  
Structural Basis

Reading the phosphorylation code: binding of the 14-3-3 protein to multivalent client phosphoproteins

2020 ◽  
Vol 477 (7) ◽  
pp. 1219-1225 ◽  
Author(s):  
Nikolai N. Sluchanko
Keyword(s):  
Protein Function ◽  
Intrinsically Disordered Protein ◽  
Structural Basis ◽  
Major Protein ◽  
Post Translational Modifications ◽  
Protein Protein Interaction ◽  
Intrinsically Disordered ◽  
Biochemical Journal ◽  
Multiple Binding ◽  
And Control

Many major protein–protein interaction networks are maintained by ‘hub’ proteins with multiple binding partners, where interactions are often facilitated by intrinsically disordered protein regions that undergo post-translational modifications, such as phosphorylation. Phosphorylation can directly affect protein function and control recognition by proteins that ‘read’ the phosphorylation code, re-wiring the interactome. The eukaryotic 14-3-3 proteins recognizing multiple phosphoproteins nicely exemplify these concepts. Although recent studies established the biochemical and structural basis for the interaction of the 14-3-3 dimers with several phosphorylated clients, understanding their assembly with partners phosphorylated at multiple sites represents a challenge. Suboptimal sequence context around the phosphorylated residue may reduce binding affinity, resulting in quantitative differences for distinct phosphorylation sites, making hierarchy and priority in their binding rather uncertain. Recently, Stevers et al. [Biochemical Journal (2017) 474: 1273–1287] undertook a remarkable attempt to untangle the mechanism of 14-3-3 dimer binding to leucine-rich repeat kinase 2 (LRRK2) that contains multiple candidate 14-3-3-binding sites and is mutated in Parkinson's disease. By using the protein-peptide binding approach, the authors systematically analyzed affinities for a set of LRRK2 phosphopeptides, alone or in combination, to a 14-3-3 protein and determined crystal structures for 14-3-3 complexes with selected phosphopeptides. This study addresses a long-standing question in the 14-3-3 biology, unearthing a range of important details that are relevant for understanding binding mechanisms of other polyvalent proteins.

scholarly journals Structural basis for molecular recognition of folic acid by folate receptors

Nature ◽  
2013 ◽  
Vol 500 (7463) ◽  
pp. 486-489 ◽  
Author(s):  
Chen Chen ◽  
Jiyuan Ke ◽  
X. Edward Zhou ◽  
Wei Yi ◽  
Joseph S. Brunzelle ◽  
...  
Keyword(s):  
Folic Acid ◽  
Molecular Recognition ◽  
Structural Basis ◽  
Folate Receptors

scholarly journals Histone transfer among chaperones

2012 ◽  
Vol 40 (2) ◽  
pp. 357-363 ◽  
Author(s):  
Wallace H. Liu ◽  
Mair E.A. Churchill
Keyword(s):  
Histone H3 ◽  
Histone Chaperone ◽  
Chromatin Assembly ◽  
Histone Chaperones ◽  
Nucleosome Assembly ◽  
Post Translational Modifications ◽  
Chromatin Dynamics ◽  
Nucleosomal Dna ◽  
Chaperone Interactions ◽  
Dependent Processes

The eukaryotic processes of nucleosome assembly and disassembly govern chromatin dynamics, in which histones exchange in a highly regulated manner to promote genome accessibility for all DNA-dependent processes. This regulation is partly carried out by histone chaperones, which serve multifaceted roles in co-ordinating the interactions of histone proteins with modification enzymes, nucleosome remodellers, other histone chaperones and nucleosomal DNA. The molecular details of the processes by which histone chaperones promote delivery of histones among their many functional partners are still largely undefined, but promise to offer insights into epigenome maintenance. In the present paper, we review recent findings on the histone chaperone interactions that guide the assembly of histones H3 and H4 into chromatin. This evidence supports the concepts of histone post-translational modifications and specific histone chaperone interactions as guiding principles for histone H3/H4 transactions during chromatin assembly.

scholarly journals Structural Basis of LSD1-CoREST Selectivity in Histone H3 Recognition

2007 ◽  
Vol 282 (28) ◽  
pp. 20070-20074 ◽  
Author(s):  
Federico Forneris ◽  
Claudia Binda ◽  
Antonio Adamo ◽  
Elena Battaglioli ◽  
Andrea Mattevi
Keyword(s):  
Histone H3 ◽  
Structural Basis
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