دورية أكاديمية
Structural insights into acetylated histone ligand recognition by the BDP1 bromodomain of Plasmodium falciparum.
العنوان: | Structural insights into acetylated histone ligand recognition by the BDP1 bromodomain of Plasmodium falciparum. |
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المؤلفون: | Singh AK; Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA., Phillips M; Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA., Alkrimi S; Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT 05446, USA., Tonelli M; NMRFAM and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA., Boyson SP; Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT 05446, USA., Malone KL; Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA., Nix JC; Molecular Biology Consortium, Advanced Light Source, Berkeley, CA 94720, USA., Glass KC; Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA; Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT 05446, USA. Electronic address: karen.glass@med.uvm.edu. |
المصدر: | International journal of biological macromolecules [Int J Biol Macromol] 2022 Dec 31; Vol. 223 (Pt A), pp. 316-326. Date of Electronic Publication: 2022 Oct 31. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Guildford, Eng., IPC Science and Technology Press. |
مواضيع طبية MeSH: | Histones*/metabolism , Plasmodium falciparum*/metabolism, Humans ; Ligands ; Protein Binding ; Protein Domains ; Acetylation ; Transcription Factor TFIIIB/metabolism |
مستخلص: | Plasmodium falciparum requires a two-host system, moving between Anopheles mosquito and humans, to complete its life cycle. To overcome such dynamic growth conditions its histones undergo various post-translational modifications to regulate gene expression. The P. falciparum Bromodomain Protein 1 (PfBDP1) has been shown to interact with acetylated lysine modifications on histone H3 to regulate the expression of invasion-related genes. Here, we investigated the ability of the PfBDP1 bromodomain to interact with acetyllsyine modifications on additional core and variant histones. A crystal structure of the PfBDP1 bromodomain (PfBDP1-BRD) reveals it contains the conserved bromodomain fold, but our comparative analysis between the PfBDP1-BRD and human bromodomain families indicates it has a unique binding mechanism. Solution NMR spectroscopy and ITC binding assays carried out with acetylated histone ligands demonstrate that it preferentially recognizes tetra-acetylated histone H4, and we detected weaker interactions with multi-acetylated H2A.Z in addition to the previously reported interactions with acetylated histone H3. Our findings indicate PfBDP1 may play additional roles in the P. falciparum life cycle, and the distinctive features of its bromodomain binding pocket could be leveraged for the development of new therapeutic agents to help overcome the continuously evolving resistance of P. falciparum against currently available drugs. Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.) |
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معلومات مُعتمدة: | P20 GM103449 United States GM NIGMS NIH HHS; P30 GM124169 United States GM NIGMS NIH HHS; R24 GM141526 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: Bromodomain (BRD); Chromatin reader domains; Epigenetics; Histones; Isothermal Titration Calorimetry (ITC); Malaria; Nuclear Magnetic Resonance (NMR); P. falciparum bromodomain-containing protein 1 (PfBDP1); Plasmodium falciparum (P. falciparum); Post-translational modifications (PTM); X-ray crystallography |
المشرفين على المادة: | 0 (Histones) 0 (Ligands) 0 (BDP1 protein, human) 0 (Transcription Factor TFIIIB) |
تواريخ الأحداث: | Date Created: 20221103 Date Completed: 20221216 Latest Revision: 20230413 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC10093686 |
DOI: | 10.1016/j.ijbiomac.2022.10.247 |
PMID: | 36328269 |
قاعدة البيانات: | MEDLINE |
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