Bacterial collagenase harnesses collagen geometry for processive cleavage.

Area of Science:

• Biochemistry
• Structural Biology
• Microbiology

Background:

• Collagen is a crucial structural protein in the extracellular matrix, forming a stable triple helix resistant to degradation.
• Flesh-eating bacteria possess collagenases that break down collagen, but the mechanism remains poorly understood.
• Understanding bacterial collagen degradation is vital for developing therapeutic strategies against infections.

Purpose of the Study:

• To elucidate the molecular mechanism by which *Hathewaya histolytica* collagenase ColH degrades collagen.
• To reveal how ColH interacts with and unwinds the collagen triple helix for processive cleavage.

Main Methods:

• Cryo-electron microscopy was employed to visualize the collagenase-substrate complex.
• Analysis of enzyme dynamics and domain movements during substrate engagement and catalysis.

Main Results:

• ColH forms a closed ring around the collagen triple helix, destabilizing it through dehydration and dynamic motions.
• Substrate-assisted twisting induces a rigid conformation, allowing one collagen chain to be threaded into the active site for cleavage.
• The enzyme likely cycles between dynamic and rigid states for sequential tripeptide degradation, utilizing uncut strands as guides.

Conclusions:

• ColH employs a novel mechanism for collagen degradation, distinct from mammalian collagenases.
• The enzyme exploits collagen's inherent helical structure for efficient and processive breakdown.
• This study reveals a unique bacterial strategy for degrading a resilient biological substrate.