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Crystal structure of malaria parasite nucleosome assembly protein: distinct modes of protein localization and histone recognition.

Gill J, Yogavel M, Kumar A, Belrhali H, Jain SK, Rug M, Brown M, Maier AG, Sharma A - J. Biol. Chem. (2009)

Bottom Line: Expression of green fluorescent protein-tagged PfNapL confirmed its exclusive localization to the parasite cytoplasm.A detailed analysis of PfNapL structure suggests unique histone binding properties.The crucial structural differences observed between parasite and yeast NAPs shed light on possible new modes of histone recognition by nucleosome assembly proteins.

View Article: PubMed Central - PubMed

Affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Road, New Delhi 110067, India.

ABSTRACT
Nucleosome assembly proteins (NAPs) are histone chaperones that are essential for the transfer and incorporation of histones into nucleosomes. NAPs participate in assembly and disassembly of nucleosomes and in chromatin structure organization. Human malaria parasite Plasmodium falciparum contains two nucleosome assembly proteins termed PfNapL and PfNapS. To gain structural insights into the mechanism of NAPs, we have determined and analyzed the crystal structure of PfNapL at 2.3 A resolution. PfNapL, an ortholog of eukaryotic NAPs, is dimeric in nature and adopts a characteristic fold seen previously for yeast NAP-1 and Vps75 and for human SET/TAF-1b (beta)/INHAT. The PfNapL monomer is comprised of domain I, containing a dimerization alpha-helix, and a domain II, composed of alpha-helices and a beta-subdomain. Structural comparisons reveal that the "accessory domain," which is inserted between the domain I and domain II in yeast NAP-1 and other eukaryotic NAPs, is surprisingly absent in PfNapL. Expression of green fluorescent protein-tagged PfNapL confirmed its exclusive localization to the parasite cytoplasm. Attempts to disrupt the PfNapL gene were not successful, indicating its essential role for the malaria parasite. A detailed analysis of PfNapL structure suggests unique histone binding properties. The crucial structural differences observed between parasite and yeast NAPs shed light on possible new modes of histone recognition by nucleosome assembly proteins.

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Electrostatic potential distribution of the PfNapL dimer. The convex region of the dimerization helix α2 contains acidic residues scattered on the surface in an alternate manner. Domain II of PfNapL forms a cavity consisting of mostly acidic residues that are conserved with yNAP-1 and hSET.
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fig5: Electrostatic potential distribution of the PfNapL dimer. The convex region of the dimerization helix α2 contains acidic residues scattered on the surface in an alternate manner. Domain II of PfNapL forms a cavity consisting of mostly acidic residues that are conserved with yNAP-1 and hSET.

Mentions: The Electrostatic Potential of PfNapL Dimer—Analysis of the electrostatic potential of PfNapL dimer indicates that the convex region of the dimerization helix α2 has acidic residues scattered on the surface in an alternate manner (Glu38, Glu41, Glu52, Asp55, Glu63, Asp80, and Glu84) (Fig. 5). There are also three basic residues toward the end of this helix (Lys70, Lys81, and Arg82) contributing to a slightly basic nature and hence an uneven charge distribution (Fig. 5). The domain II of PfNapL dimer has a hydrophobic nature on one side and is highly negatively charged on the opposite face with several residues (Glu119, Glu122, Glu123, Glu252, Glu256, Asp258, Glu260, and Glu267), forming a cavity that is also a characteristic feature of the yNAP-1 and hSET (Fig. 5). The bottom of this cavity has an uneven charge character, and a single acidic residue, Glu61, is present at its base. It has been previously suggested for yNAP-1 that this highly acidic cavity might be important for binding to basic histones (15). The residues Asp119, Glu122, Glu123, Asp258, Glu260, and Glu267 that constitute this cavity in PfNapL are structurally conserved with yNAP-1 and hSET, hence highlighting their possible significance.


Crystal structure of malaria parasite nucleosome assembly protein: distinct modes of protein localization and histone recognition.

Gill J, Yogavel M, Kumar A, Belrhali H, Jain SK, Rug M, Brown M, Maier AG, Sharma A - J. Biol. Chem. (2009)

Electrostatic potential distribution of the PfNapL dimer. The convex region of the dimerization helix α2 contains acidic residues scattered on the surface in an alternate manner. Domain II of PfNapL forms a cavity consisting of mostly acidic residues that are conserved with yNAP-1 and hSET.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2665062&req=5

fig5: Electrostatic potential distribution of the PfNapL dimer. The convex region of the dimerization helix α2 contains acidic residues scattered on the surface in an alternate manner. Domain II of PfNapL forms a cavity consisting of mostly acidic residues that are conserved with yNAP-1 and hSET.
Mentions: The Electrostatic Potential of PfNapL Dimer—Analysis of the electrostatic potential of PfNapL dimer indicates that the convex region of the dimerization helix α2 has acidic residues scattered on the surface in an alternate manner (Glu38, Glu41, Glu52, Asp55, Glu63, Asp80, and Glu84) (Fig. 5). There are also three basic residues toward the end of this helix (Lys70, Lys81, and Arg82) contributing to a slightly basic nature and hence an uneven charge distribution (Fig. 5). The domain II of PfNapL dimer has a hydrophobic nature on one side and is highly negatively charged on the opposite face with several residues (Glu119, Glu122, Glu123, Glu252, Glu256, Asp258, Glu260, and Glu267), forming a cavity that is also a characteristic feature of the yNAP-1 and hSET (Fig. 5). The bottom of this cavity has an uneven charge character, and a single acidic residue, Glu61, is present at its base. It has been previously suggested for yNAP-1 that this highly acidic cavity might be important for binding to basic histones (15). The residues Asp119, Glu122, Glu123, Asp258, Glu260, and Glu267 that constitute this cavity in PfNapL are structurally conserved with yNAP-1 and hSET, hence highlighting their possible significance.

Bottom Line: Expression of green fluorescent protein-tagged PfNapL confirmed its exclusive localization to the parasite cytoplasm.A detailed analysis of PfNapL structure suggests unique histone binding properties.The crucial structural differences observed between parasite and yeast NAPs shed light on possible new modes of histone recognition by nucleosome assembly proteins.

View Article: PubMed Central - PubMed

Affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Road, New Delhi 110067, India.

ABSTRACT
Nucleosome assembly proteins (NAPs) are histone chaperones that are essential for the transfer and incorporation of histones into nucleosomes. NAPs participate in assembly and disassembly of nucleosomes and in chromatin structure organization. Human malaria parasite Plasmodium falciparum contains two nucleosome assembly proteins termed PfNapL and PfNapS. To gain structural insights into the mechanism of NAPs, we have determined and analyzed the crystal structure of PfNapL at 2.3 A resolution. PfNapL, an ortholog of eukaryotic NAPs, is dimeric in nature and adopts a characteristic fold seen previously for yeast NAP-1 and Vps75 and for human SET/TAF-1b (beta)/INHAT. The PfNapL monomer is comprised of domain I, containing a dimerization alpha-helix, and a domain II, composed of alpha-helices and a beta-subdomain. Structural comparisons reveal that the "accessory domain," which is inserted between the domain I and domain II in yeast NAP-1 and other eukaryotic NAPs, is surprisingly absent in PfNapL. Expression of green fluorescent protein-tagged PfNapL confirmed its exclusive localization to the parasite cytoplasm. Attempts to disrupt the PfNapL gene were not successful, indicating its essential role for the malaria parasite. A detailed analysis of PfNapL structure suggests unique histone binding properties. The crucial structural differences observed between parasite and yeast NAPs shed light on possible new modes of histone recognition by nucleosome assembly proteins.

Show MeSH
Related in: MedlinePlus