Structural basis for Zn2+-dependent intercellular adhesion in staphylococcal biofilms

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Staphylococcal bacteria, including Staphylococcus epidermidis and Staphylococcus aureus, are significant causes of chronic biofilm-related infections.
• The proteins Aap (in S. epidermidis) and SasG (in S. aureus) are crucial for mediating biofilm formation in these bacteria.
• The self-association of Aap and SasG, facilitated by Zn(2+), is essential for establishing extensive intercellular adhesion.

Purpose of the Study:

• To determine the crystal structure of a Zn(2+)-bound construct from the self-associating region of the Aap protein.
• To elucidate the structural mechanisms underlying Zn(2+)-dependent self-association and intercellular adhesion mediated by Aap.

Main Methods:

• X-ray crystallography was employed to obtain the crystal structure of the Zn(2+)-bound Aap construct.
• Analysis of multiple crystal forms to observe Zn(2+)-dependent dimer formation and coordination.

Main Results:

• The crystal structure revealed unusual features, including elongated, solvent-exposed β-sheets and a lack of a canonical hydrophobic core.
• Zn(2+)-dependent dimers of Aap were observed in three distinct crystal forms.
• The formation of these dimers involves pleomorphic coordination of Zn(2+) across the dimer interface, facilitating trans-dimerization.

Conclusions:

• The determined structures provide insights into how long, flexible surface proteins like Aap can form strong intercellular adhesion sites.
• This mechanism is critical for bacterial survival and infection under challenging environmental conditions.
• Understanding these structural details can inform strategies to combat biofilm-related staphylococcal infections.