Matrix metalloproteinases: structures, evolution, and diversification

Area of Science:

• Biochemistry
• Evolutionary Biology
• Structural Biology

Background:

• Matrix metalloproteinases (MMPs) are a diverse family of enzymes involved in extracellular matrix remodeling.
• Understanding the evolutionary history and structural diversity of MMPs is crucial for comprehending their biological roles.

Purpose of the Study:

• To perform a comprehensive sequence alignment of 64 matrix metalloproteinases (MMPs) across various species.
• To correlate sequence data with structural information of catalytic domains.
• To elucidate the evolutionary pathways and subfamily diversification within the MMP family.

Main Methods:

• Sequence alignment of entire MMP sequences and their catalytic/hemopexin-like domains.
• Comparative analysis of 64 MMPs from plants, invertebrates, and vertebrates.
• Correlation of sequence data with crystallographic and computational structural data for 23 representative MMPs.
• Survey of metal-binding sites and substrate-interaction loops.

Main Results:

• Identification of 23 distinct MMP subfamilies.
• Detailed analysis of conserved and variable regions, including metal-binding sites and substrate-interaction loops.
• Evidence supporting early domain assembly as a key evolutionary event.
• Observation of parallel diversification among MMP subfamilies.
• Proposal of retrograde structure simplification in the evolution of simpler MMPs like matrilysin.

Conclusions:

• The assembly of domains into multidomain enzymes was an early evolutionary event in MMPs.
• Subsequent diversification occurred in parallel across different MMP lineages.
• MMPs with simple domain structures likely evolved from more complex ancestors through simplification.