Faculty Collaboration Database

Structural insights into histone chaperone Asf1 and its characterization from Plasmodium falciparum. Biochem J 2021 Mar 12;478(5):1117-1136

Date

01/28/2021

Pubmed ID

33501928

DOI

10.1042/BCJ20200891

Scopus ID

2-s2.0-85102965209 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Asf1 is a highly conserved histone chaperone that regulates tightly coupled nucleosome assembly/disassembly process. We observed that Plasmodium falciparum Asf1 (PfAsf1) is ubiquitously expressed in different stages of the life cycle of the parasite. To gain further insight into its biological activity, we solved the structure of N-terminal histone chaperone domain of PfAsf1 (1-159 amino acids) by X-ray crystallography to a resolution of 2.4 Å. The structure is composed of two beta-sheet to form a beta-sandwich, which resembles an immunoglobulin-like fold. The surface-charge distribution of PfAsf1 is distinct from yAsf1 and hAsf1 although the core-structure shows significant similarity. The crystal-structure indicated that PfAsf1 may exist in a dimeric-state which was further confirmed by solution cross-linking experiment. PfAsf1 was found to specifically interact with Plasmodium histone H3 and H4 and was able to deposit H3/H4 dimer onto DNA-template to form disomes, showing its characteristic histone chaperone activity. We mapped the critical residues of PfAsf1 involved in histone H3/H4 interaction and confirmed by site-directed mutagenesis. Further analysis indicates that histone interacting surface of Asf1 is highly conserved while the dimerization interface is variable. Our results identify the role of PfAsf1 as a mediator of chromatin assembly in Plasmodium falciparum, which is the causative agent of malignant malaria in humans.

Author List

Srivastava DK, Gunjan S, Das C, Seshadri V, Roy S

Author

Sarika Gunjan PhD Postdoctoral Researcher 2 in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Chromatin Assembly and Disassembly
Crystallography, X-Ray
DNA Replication
Erythrocytes
Evolution, Molecular
Histone Chaperones
Histones
Humans
Models, Molecular
Phylogeny
Plasmodium falciparum
Protein Conformation
Protozoan Proteins
Sequence Homology