Structure based hyperthermostability of archaeal histone HPhA from Pyrococcus horikoshii

J Mol Biol. 2003 Jan 31;325(5):1031-7. doi: 10.1016/s0022-2836(02)01285-8.

Abstract

The histone protein HPhA from the hyperthermophilic archaeon Pyrococcus horikoshii, shows hyperthermostability, as required for optimal growth of the organism at 95 degrees C. The structure of recombinant P.horikoshii HPhA has been determined to 2.3A resolution by molecular replacement, and refined to R(work) and R(free) values of 20.7% and 27.3%, respectively. The HPhA monomer structure is characterized by the histone fold and assembles into a homodimer like other archaeal histones. There are four anions found in the dimer structure, giving rise to clues as to where DNA might bind. A detailed comparison of four known structures of archaeal histones, which evolve and exist under different temperatures, shows that the thermophilic archaeal histone HPhA has a larger hydrophobic contact area, an increased number of hydrogen bonds and a reduced solvent-accessible area. We also observe a unique network of tyrosine residues located at the crossover point of the two HPhA monomers, which locks them together and stabilizes the dimer. These factors together account for the increased thermal stability.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Archaea / chemistry*
  • Crystallization
  • Dimerization
  • Escherichia coli / metabolism
  • Histones / chemistry*
  • Histones / metabolism
  • Hydrogen Bonding
  • Molecular Sequence Data
  • Phosphotransferases (Alcohol Group Acceptor)
  • Protein Conformation
  • Pyrococcus / chemistry*
  • Pyrococcus / metabolism
  • Sequence Homology, Amino Acid
  • Temperature*
  • X-Ray Diffraction

Substances

  • Histones
  • Phosphotransferases (Alcohol Group Acceptor)
  • hygromycin-B kinase

Associated data

  • PDB/1KU5