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Histone octamer helical tubes suggest that an internucleosomal four-helix bundle stabilizes the chromatin fiber.

ABSTRACT: A major question in chromatin involves the exact organization of nucleosomes within the 30-nm chromatin fiber and its structural determinants of assembly. Here we investigate the structure of histone octamer helical tubes via the method of iterative helical real-space reconstruction. Accurate placement of the x-ray structure of the histone octamer within the reconstructed density yields a pseudoatomic model for the entire helix, and allows precise identification of molecular interactions between neighboring octamers. One such interaction that would not be obscured by DNA in the nucleosome consists of a twofold symmetric four-helix bundle formed between pairs of H2B-alpha3 and H2B-alphaC helices of neighboring octamers. We believe that this interface can act as an internucleosomal four-helix bundle within the context of the chromatin fiber. The potential relevance of this interface in the folding of the 30-nm chromatin fiber is discussed.

SUBMITTER: Frouws TD

PROVIDER: S-EPMC2718273 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Histone octamer helical tubes suggest that an internucleosomal four-helix bundle stabilizes the chromatin fiber.

Frouws Timothy D TD Patterton Hugh-G HG Sewell Bryan T BT

Biophysical journal 20090401 8

A major question in chromatin involves the exact organization of nucleosomes within the 30-nm chromatin fiber and its structural determinants of assembly. Here we investigate the structure of histone octamer helical tubes via the method of iterative helical real-space reconstruction. Accurate placement of the x-ray structure of the histone octamer within the reconstructed density yields a pseudoatomic model for the entire helix, and allows precise identification of molecular interactions between ...[more]

PMID: 19383479

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Project description:De novo protein design represents an attractive approach for testing and extending our understanding of metalloprotein structure and function. Here, we describe our work on the design of DF (Due Ferri or two-iron in Italian), a minimalist model for the active sites of much larger and more complex natural diiron and dimanganese proteins. In nature, diiron and dimanganese proteins protypically bind their ions in 4-Glu, 2-His environments, and they catalyze diverse reactions, ranging from hydrolysis, to O2-dependent chemistry, to decarbonylation of aldehydes. In the design of DF, the position of each atom-including the backbone, the first-shell ligands, the second-shell hydrogen-bonded groups, and the well-packed hydrophobic core-was bespoke using precise mathematical equations and chemical principles. The first member of the DF family was designed to be of minimal size and complexity and yet to display the quintessential elements required for binding the dimetal cofactor. After thoroughly characterizing its structural, dynamic, spectroscopic, and functional properties, we added additional complexity in a rational stepwise manner to achieve increasingly sophisticated catalytic functions, ultimately demonstrating substrate-gated four-electron reduction of O2 to water. We also briefly describe the extension of these studies to the design of proteins that bind nonbiological metal cofactors (a synthetic porphyrin and a tetranuclear cluster), and a Zn2+/proton antiporting membrane protein. Together these studies demonstrate a successful and generally applicable strategy for de novo metalloprotein design, which might indeed mimic the process by which primordial metalloproteins evolved. We began the design process with a highly symmetrical backbone and binding site, by using point-group symmetry to assemble the secondary structures that position the amino acid side chains required for binding. The resulting models provided a rough starting point and initial parameters for the subsequent precise design of the final protein using modern methods of computational protein design. Unless the desired site is itself symmetrical, this process requires reduction of the symmetry or lifting it altogether. Nevertheless, the initial symmetrical structure can be helpful to restrain the search space during assembly of the backbone. Finally, the methods described here should be generally applicable to the design of highly stable and robust catalysts and sensors. There is considerable potential in combining the efficiency and knowledge base associated with homogeneous metal catalysis with the programmability, biocompatibility, and versatility of proteins. While the work reported here focuses on testing and learning the principles of natural metalloproteins by designing and studying proteins one at a time, there is also considerable potential for using designed proteins that incorporate both biological and nonbiological metal ion cofactors for the evolution of novel catalysts.

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Histone octamer helical tubes suggest that an internucleosomal four-helix bundle stabilizes the chromatin fiber.

Publications

Histone octamer helical tubes suggest that an internucleosomal four-helix bundle stabilizes the chromatin fiber.

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