Structure, localization and histone binding properties of nuclear-associated nucleosome assembly protein from Plasmodium falciparum
1 Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Road, New Delhi, 110067, India
2 European Molecular Biology Laboratory (EMBL), 6 rue Jules Horowitz, BP 181, F-38042 Grenoble Cedex 9, France
3 Department of Biotechnology, Jamia Hamdard, New Delhi 110062, India
4 Malaria Functional Genomics Facility, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne 3050, Australia
5 Biochemistry Department, La Trobe University, Melbourne 3086, Australia
Malaria Journal 2010, 9:90 doi:10.1186/1475-2875-9-90Published: 8 April 2010
Nucleosome assembly proteins (NAPs) are histone chaperones that are crucial for the shuttling and incorporation of histones into nucleosomes. NAPs participate in the assembly and disassembly of nucleosomes thus contributing to chromatin structure organization. The human malaria parasite Plasmodium falciparum contains two nucleosome assembly proteins termed PfNapL and PfNapS.
Three-dimensional crystal structure of PfNapS has been determined and analysed. Gene knockout and localization studies were also performed on PfNapS using transfection studies. Fluorescence spectroscopy was performed to identify histone-binding sites on PfNapS. Extensive sequence and structural comparisons were done with the crystal structures available for NAP/SET family of proteins.
Crystal structure of PfNapS shares structural similarity with previous structures from NAP/SET family. Failed attempts to knock-out the gene for PfNapS from malaria parasite suggest essentiality in the parasite. GFP-fused PfNapS fusion protein targeting indicates cellular localization of PfNapS in the parasite nucleus. Fluorescence spectroscopy data suggest that PfNapS interacts with core histones (tetramer, octamer, H3, H4, H2A and H2B) at a different site from its interaction with linker histone H1. This analysis illustrates two regions on the PfNapS dimer as the possible sites for histone recognition.
This work presents a thorough analysis of the structural, functional and regulatory attributes of PfNapS from P. falciparum with respect to previously studied histone chaperones.