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Comparative Study
. 2001 Oct;10(10):2002-7.
doi: 10.1110/ps.10901.

An ancestral nuclear protein assembly: crystal structure of the Methanopyrus kandleri histone

R L Fahrner  1 , D Cascio, J A Lake, A Slesarev
Affiliations
Comparative Study

An ancestral nuclear protein assembly: crystal structure of the Methanopyrus kandleri histone

R L Fahrner et al. Protein Sci. 2001 Oct.

Abstract

Eukaryotic histone proteins condense DNA into compact structures called nucleosomes. Nucleosomes were viewed as a distinguishing feature of eukaryotes prior to identification of histone orthologs in methanogens. Although evolutionarily distinct from methanogens, the methane-producing hyperthermophile Methanopyrus kandleri produces a novel, 154-residue histone (HMk). Amino acid sequence comparisons show that HMk differs from both methanogenic and eukaryotic histones, in that it contains two histone-fold ms within a single chain. The two HMk histone-fold ms, N and C terminal, are 28% identical in amino acid sequence to each other and approximately 21% identical in amino acid sequence to other histone proteins. Here we present the 1.37-A-resolution crystal structure of HMk and report that the HMk monomer structure is homologous to the eukaryotic histone heterodimers. In the crystal, HMk forms a dimer homologous to [H3-H4](2) in the eukaryotic nucleosome. Based on the spatial similarities to structural ms found in the eukaryotic nucleosome that are important for DNA-binding, we infer that the Methanopyrus histone binds DNA in a manner similar to the eukaryotic histone tetramer [H3-H4](2).

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Figures

Fig. 1.
Fig. 1.
(A) Ribbon diagram of the HMk monomer structure. α-Helices are depicted in cyan, β-sheets in green, and coils in orange. Helices are labeled at their N termini as follows: the helices in domain 1, the N-terminal domain, are denoted α1N, α2N, and α3N; the helices in domain 2, the C-terminal domain, are denoted α1C, α2C, and α3C. Note the orange loop connecting the two domains that wraps behind the molecule at about the center of the molecule. Also note the short, parallel β-sheets located at both ends of the long molecular axis. (B) Ribbon diagram of the HMk dimer. α-Helices are depicted in cyan, β-sheets in green, and coils in orange. The four-helix bundle formed by the dimer interface is visible at the top center of the molecule.
Fig. 2.
Fig. 2.
Nomenclature and schematic representation of assemblies observed for several histones. The histone fold is stylized here as a pointed N terminus representing the short helix 1, a long central region representing the longer helix 2, and a rounded C terminus representing the short helix 3. A eukaryotic nucleosome is comprised of 145–147 bp of DNA and two copies each of four histone proteins (H2A, H2B, H3, and H4) (Thomas and Kornberg 1975; Arents and Moudrianakis 1995; Luger et al. 1997). A complete nucleosome histone octomer may be viewed as a left-handed spiral protein assembly constructed from three subassemblies. (A) (Left) An HMk monomer contains two histone-fold ms, the N- and C-terminal domains, tethered by a 13-residue loop. (Right) An HMk dimer formed through crystallographic contacts associates through C-terminal helices of the N-terminal domain. (B) (Left) The eight histone proteins assemble as two copies each of two different heterodimers (H2A–H2B and H3–H4) (Thomas and Kornberg 1975; Luger et al. 1997). (Center) [H3–H4] assembles as [H3–H4]2. This complex initiates DNA-binding, positions the nucleosome, and forms stable nucleosomelike structures in complex with DNA (Dong and van Holde 1991; Hayes et al. 1991). (Right) The nucleosome is completed by adding [H2A–H2B] to each end of the [H3–H4]2 tetramer.
Fig. 3.
Fig. 3.
Sequence alignments based upon structure alignments for various histones. Only the histone-fold segments are shown. Residues buried in the dimerization interfaces are colored HMk N- and C-terminal domains (cyan), HMfB homodimer (purple), H2A–H2B (yellow), and H3–H4 (orange). Residues buried in the four-helix-bundle interface are colored HMk (dark blue); H2B, H3, and H4 (red). Some charged residues important in DNA interactions in the eukaryotic histone α1α1 m are indicated in aqua, and the region is denoted by α1 at the top of the alignments. The corresponding residues for methanogen histones are also indicated in aqua. The Arg–Thr pairs that form the L1L2 ms are colored in aqua and are indicated by an arrow at the bottom of the alignments. Helical regions are underlined. Loop 2 salt bridges are illustrated by schematic side chains. This figure is similar in style to a figure that appeared in Luger et al. 1997.
Fig. 4.
Fig. 4.
Ribbon diagrams of HMk (cyan) aligned to various histone proteins. (A) HMk aligned to H2A–H2B (Luger et al. 1997). (B) HMk aligned to H3–H4 (Luger et al. 1997). (C) C-Terminal domain of HMk aligned to HMfB (Starich et al. 1996). (D) Superposition of HMk dimer created from the crystallographic 2-fold axis (cyan) and (H3–H4)2 tetramer. Note the structural similarity between HMk and the other histones. Also note the similar arrangement of domains and interfaces between HMk and [H3–H4]. However, in the HMk structure, the C termini contact one another, whereas in the nucleosome structure the [H3–H4]2 has a gap. Structure alignments were performed using ALIGN (Satow et al. 1986).
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