Crystal structure of histone chaperone Vps75 from Candida albicans

Area of Science:

• Structural Biology
• Mycology
• Biochemistry

Background:

• Vps75 is a histone chaperone that interacts with Rtt109, a fungal-specific histone acetyltransferase.
• This interaction stimulates Rtt109's acetylation activity on histone H3, a crucial epigenetic modification.
• Candida albicans is a significant fungal pathogen, making its molecular mechanisms of interest.

Purpose of the Study:

• To determine the crystal structure of Vps75 from Candida albicans (CaVps75).
• To elucidate the structural features of CaVps75 and compare them to known Vps75 structures.
• To understand the potential role of CaVps75 in histone modification within C. albicans.

Main Methods:

• X-ray crystallography was used to obtain the high-resolution structure of CaVps75.
• Biochemical assays were employed to investigate CaVps75's oligomerization behavior in solution.
• Structural comparisons were made with Vps75 from other species, particularly yeast.

Main Results:

• CaVps75 forms a headphone-like dimer with a large negatively charged concave surface, suggesting histone binding.
• The dimer possesses positively charged distal ends and an additional alpha helix compared to yeast Vps75.
• CaVps75 displays concentration- and ionic strength-dependent higher-order oligomerization.
• A unique inter-dimer interaction mediated by electrostatic forces was observed in the crystal structure.

Conclusions:

• The unique structural features of CaVps75, including its dimerization and charged surfaces, likely facilitate its interaction with histones.
• The observed oligomerization and inter-dimer interactions may play a role in regulating Vps75 function in C. albicans.
• This structural information provides a foundation for understanding Vps75's role in the biology of this important fungal pathogen.