Class I histone deacetylase complex: Structure and functional correlates.

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• The Schizosaccharomyces pombe Clr6S complex is a class I histone deacetylase.
• It functions as a zinc-dependent enzyme, removing acetyl groups from histone tails.
• Histone deacetylation plays a critical role in gene regulation.

Purpose of the Study:

• To determine the cryo-electron microscopy (cryo-EM) structure of the Clr6S complex alone.
• To elucidate the cryo-EM structure of the Clr6S complex in complex with a nucleosome.
• To understand the structural basis of Clr6S catalytic activity and substrate interaction.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to obtain high-resolution structures.
• The structure of Clr6S alone was determined.
• The structure of Clr6S in complex with a nucleosome was also mapped.

Main Results:

• The near-atomic resolution cryo-EM structure revealed the active center of Clr6S.
• Key catalytic features include a zinc-coordinated water molecule and a substrate-positioning loop.
• The Clr6S-nucleosome complex map showed multiple interaction sites and significant relative motion, suggesting flexibility.

Conclusions:

• The revealed active site provides insights into the catalytic mechanism of Clr6S.
• The observed flexibility in the Clr6S-nucleosome complex is likely essential for the enzyme's function.
• These findings contribute to understanding histone deacetylation in Schizosaccharomyces pombe.