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5ULC PLASMODIUM FALCIPARUM BROMODOMAIN-CONTAINING PROTEIN PF10_0328

This is a default text for your page Saleh Alkrimi/ Sandbox 898. Click above on edit this page to modify. Be careful with the < and > signs.

You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

1 Introduction
2 Structure Features
3 Bromodomain Histone Ligand Recognition
4 Function
5 Sequence alignment
6 Conservation
7 Evolutionary Conservation
8 Medical Important

Introduction

plays a key role in the coordinate regulation of genes involved in erythrocyte invasion and thus in the proliferation of malaria parasites. PfBDP1 regulates invasion-related gene expression through binding to acetylated histones present in nucleosomes at regulatory sites^[3]. Bromodomains are evolutionarily conserved protein modules that specifically recognize acetylated lysine residues on histone tails of the nucleosome. During red-blood-cell-stage infection of Plasmodium falciparum, the parasite undergoes repeated rounds of replication, egress, and invasion. Erythrocyte invasion involves specific interactions between host cell receptors and parasite ligands and coordinated expression of genes specific to this step of the life cycle. Parasite-specific bromodomain protein, PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes and directly controls their expression. A parasite-specific bromodomain protein, PfBDP1 is essential in malaria parasites. PfBDP1 binds to chromatin at invasion gene promoters. Depletion of PfBDP1 dysregulates invasion gene expression and disrupts invasion. PfBDP1 as a critical activator of the coordinate expression of genes that encode proteins with an essential role in erythrocyte invasion.

Structure Features

PfBDP1 (PF3D7_1033700), is a 55 kDa protein. As shown in Figure below, the domain architecture of P. falciparum bromodomain protein 1 (PfBDP1) contains a single C-terminal bromodomain and a number of ankyrin repeats (in the N-terminal portion of the protein, presumably operating in protein-protein interactions); this architecture appears to be unique to apicomplexan parasites.

Bromodomain Histone Ligand Recognition

PfBDP1 bromodomain can recognize different acetyllysine histone ligands with varying binding affinities. Currently, it is known that PfBDP1 binds to acetylated histone H3, and it predominantly recognizes H3K9ac and H3K14ac^[4] PfBDP1 was shown to positively regulate transcription of invasion genes

Function

PfBDP1 has been shown to be involved in the regulation of invasion-related genes in asexual stage parasites. Also, it appears to be essential for parasite growth^[5]. conditional knockdown of PfBDP1 resulted in erythrocyte invasion defects and parasite growth inhibition, further confirming the essentiality of this bromodomain protein for the coordinated expression of invasion genes in P. falciparum^[6]. PfBDP1 Interacts with a Second Bromodomain Protein Bromodomain proteins generally function as part of larger complexes, where they act to recruit factors that can influence chromatin structure^[7] PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes and directly controls their expression. bromodomain protein (PfBDP1), directly exerts positive regulation of invasion genes and is required for normal erythrocyte invasion^[8].

Sequence alignment

Conservation

Evolutionary Conservation

Medical Important

The importance of the bromodomain protein PfBDP1 in regulating parasite growth and the feasibility of bromodomain inhibitors as therapeutics establish PfBDP1 as an exciting potential drug target^[9]. Malaria is a major public health problem in many developing countries, with the malignant tertian parasite Plasmodium falciparum causing the most malaria-associated mortality.

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

References

↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
↑ Gabrielle A. Josling et al., “A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression,” Cell Host & Microbe 17, no. 6 (June 10, 2015): 741–51, https://doi.org/10.1016/j.chom.2015.05.009.
↑ . bBy binding to acetylated histone H3.<ref> “The Role of Chromatin Structure in Gene Regulation of the Human Malaria Parasite,” accessed April 20, 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410391/.</li> <li id="cite_note-4">[[#cite_ref-4|↑]] “Bromodomains in Protozoan Parasites: Evolution, Function, and Opportunities for Drug Development,” accessed April 20, 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312238/.</li> <li id="cite_note-5">[[#cite_ref-5|↑]] “Activity of Bromodomain Protein Inhibitors/Binders against Asexual-Stage Plasmodium Falciparum Parasites,” accessed April 20, 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039313/.</li> <li id="cite_note-6">[[#cite_ref-6|↑]] Gabrielle A. Josling et al., “A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression,” Cell Host & Microbe 17, no. 6 (June 10, 2015): 741–51, https://doi.org/10.1016/j.chom.2015.05.009.</li> <li id="cite_note-7">[[#cite_ref-7|↑]] Joana Mendonca Santos et al., “Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor,” Cell Host & Microbe 21, no. 6 (June 14, 2017): 731-741.e10, https://doi.org/10.1016/j.chom.2017.05.006.</li> <li id="cite_note-8">[[#cite_ref-8|↑]] Gabrielle A. Josling et al., “A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression,” Cell Host & Microbe 17, no. 6 (June 10, 2015): 741–51, https://doi.org/10.1016/j.chom.2015.05.009.</li></ol></ref>

Proteopedia Page Contributors and Editors (what is this?)

Saleh Alkrimi

Retrieved from "http://52.214.119.220/wiki/index.php/User:Saleh_Alkrimi/_Sandbox_898"

@@ Line 6: / Line 6: @@
 == Introduction ==
-plays a key role in the coordinate regulation of genes involved in erythrocyte invasion and thus in the proliferation of malaria parasites. PfBDP1 regulates invasion-related gene expression through binding to acetylated histones present in nucleosomes at regulatory sites [22].
+plays a key role in the coordinate regulation of genes involved in erythrocyte invasion and thus in the proliferation of malaria parasites. PfBDP1 regulates invasion-related gene expression through binding to acetylated histones present in nucleosomes at regulatory sites<ref>Gabrielle A. Josling et al., “A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression,” Cell Host & Microbe 17, no. 6 (June 10, 2015): 741–51, https://doi.org/10.1016/j.chom.2015.05.009.</ref>.
 Bromodomains are evolutionarily conserved protein modules that specifically recognize acetylated lysine residues on histone tails of the nucleosome. During red-blood-cell-stage infection of Plasmodium falciparum, the parasite undergoes repeated rounds of replication, egress, and invasion. Erythrocyte invasion involves specific interactions between host cell receptors and parasite ligands and coordinated expression of genes specific to this step of the life cycle. Parasite-specific bromodomain protein, PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes and directly controls their expression.
 A parasite-specific bromodomain protein, PfBDP1 is essential in malaria parasites. PfBDP1 binds to chromatin at invasion gene promoters. Depletion of PfBDP1 dysregulates invasion gene expression and disrupts invasion. PfBDP1 as a critical activator of the coordinate expression of genes that encode proteins with an essential role in erythrocyte invasion.
@@ Line 17: / Line 17: @@
 == Function ==
 PfBDP1 has been shown to be involved in the regulation of invasion-related genes in asexual stage parasites. Also, it appears to be essential for parasite growth<ref> “Bromodomains in Protozoan Parasites: Evolution, Function, and Opportunities for Drug Development,” accessed April 20, 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312238/.</ref>.
-conditional knockdown of PfBDP1 resulted in erythrocyte invasion defects and parasite growth inhibition, further confirming the essentiality of this bromodomain protein for the coordinated expression of invasion genes in P. falciparum [28].
+conditional knockdown of PfBDP1 resulted in erythrocyte invasion defects and parasite growth inhibition, further confirming the essentiality of this bromodomain protein for the coordinated expression of invasion genes in P. falciparum<ref> “Activity of Bromodomain Protein Inhibitors/Binders against Asexual-Stage Plasmodium Falciparum Parasites,” accessed April 20, 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039313/.</ref>.
-PfBDP1 Interacts with a Second Bromodomain Protein Bromodomain proteins generally function as part of larger complexes, where they act to recruit factors that can influence chromatin structure [22]
+PfBDP1 Interacts with a Second Bromodomain Protein Bromodomain proteins generally function as part of larger complexes, where they act to recruit factors that can influence chromatin structure<ref>Gabrielle A. Josling et al., “A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression,” Cell Host & Microbe 17, no. 6 (June 10, 2015): 741–51, https://doi.org/10.1016/j.chom.2015.05.009.</ref>
-PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes and directly controls their expression. bromodomain protein (PfBDP1), directly exerts positive regulation of invasion genes and is required for normal erythrocyte invasion. [24]
+PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes and directly controls their expression. bromodomain protein (PfBDP1), directly exerts positive regulation of invasion genes and is required for normal erythrocyte invasion<ref> Joana Mendonca Santos et al., “Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor,” Cell Host & Microbe 21, no. 6 (June 14, 2017): 731-741.e10, https://doi.org/10.1016/j.chom.2017.05.006.</ref>.
 == Sequence alignment ==
 == Conservation ==
 == Evolutionary Conservation ==
 == Medical Important ==
-The importance of the bromodomain protein PfBDP1 in regulating parasite growth and the feasibility of bromodomain inhibitors as therapeutics establish PfBDP1 as an exciting potential drug target.[22]
+The importance of the bromodomain protein PfBDP1 in regulating parasite growth and the feasibility of bromodomain inhibitors as therapeutics establish PfBDP1 as an exciting potential drug target<ref> Gabrielle A. Josling et al., “A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression,” Cell Host & Microbe 17, no. 6 (June 10, 2015): 741–51, https://doi.org/10.1016/j.chom.2015.05.009.</ref>.
 Malaria is a major public health problem in many developing countries, with the malignant tertian parasite Plasmodium falciparum causing the most malaria-associated mortality.
-== Structural highlights ==
 This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
 </StructureSection>
 == References ==
 <references/>