A sulfilimine bond identified in collagen IV

Area of Science:

• Biochemistry
• Evolutionary Biology
• Cell Biology

Background:

• Collagen IV networks form essential basement membranes in metazoa, providing structural integrity and cell signaling.
• These networks are stabilized by covalent crosslinks, though the specific types have not been fully elucidated.
• The extracellular matrix plays a critical role in tissue development and response to environmental factors.

Purpose of the Study:

• To identify the specific covalent crosslinks stabilizing Collagen IV networks.
• To characterize the structure and evolutionary origin of novel crosslinking bonds in Collagen IV.
• To understand the role of these crosslinks in the adaptation of the extracellular matrix to mechanical stress.

Main Methods:

• Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for high-resolution mass analysis.
• Nuclear magnetic resonance (NMR) spectroscopy for detailed structural elucidation of the crosslink.
• Comparative analysis across metazoan phyla to determine evolutionary origins.

Main Results:

• Identification of a novel sulfilimine bond (-S=N-) linking hydroxylysine-211 and methionine-93 in adjacent Collagen IV protomers.
• This sulfilimine bond represents a previously undiscovered type of biomolecular linkage.
• The bond's presence suggests an evolutionary origin at the divergence of sponges and cnidarians.

Conclusions:

• The sulfilimine bond is a key stabilizing element in ancient Collagen IV networks, essential for tissue structural integrity.
• This finding reveals a novel adaptation of the extracellular matrix in response to mechanical stress during metazoan evolution.
• The discovery provides insights into the molecular mechanisms underlying tissue stability and evolution across diverse animal life.