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Updated: May 17, 2026
07:09
Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States
Published on: April 1, 2015
Correlating structure and function during the evolution of fibrinogen-related domains
Russell F Doolittle1, Kyle McNamara, Kevin Lin
1Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, California 92093-0314, USA. rdoolittle@ucsd.edu
Protein Science : a Publication of the Protein Society
|October 19, 2012
Summary
Fibrinogen-related domains (FReDs) are ancient protein structures involved in diverse functions like immunity and clotting. Their evolution reveals distinct changes, particularly in ficolins, impacting their binding capabilities.
Area of Science:
- Evolutionary biology
- Molecular biology
- Genomics
Background:
- Fibrinogen-related domains (FReDs) are conserved protein modules present in diverse animal proteins.
- These domains mediate various functions, including non-self recognition and blood clot formation.
- FReDs share a common binding surface crucial for their molecular interactions.
Purpose of the Study:
- To investigate the evolutionary history and diversification of FReDs across the animal kingdom.
- To identify the emergence and functional correlations of different FReP (FReD-containing protein) types.
- To understand the structural changes associated with functional transitions in FReDs.
Main Methods:
- Phylogenetic analysis of FRePs from 19 diverse animal genomes (sponge to deuterostomes).
- Comparative sequence and structural analysis of FReDs.
- Examination of domain interactions and their influence on FReD function.
Main Results:
- Phylogenetic reconstructions pinpoint the evolutionary origins of various FReP types.
- Specific carboxyl-terminal subdomain insertions correlate with shifts from sugar to peptide binding.
- Ficolin FReDs exhibit the fastest evolutionary rate, with significant changes in the 'P domain', unlike most other vertebrate FReDs.
- Unbalanced evolutionary change in FReDs is also observed in non-chordates, often linked to innate immunity.
Conclusions:
- FReDs have a deep evolutionary history with diversification driven by structural modifications.
- Evolutionary rates and patterns vary significantly among FReD families, with ficolins showing rapid, distinct changes.
- Understanding FReD evolution provides insights into the development of innate immunity and other biological processes.
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