DOI: 10.2174/0929866530666230726100916 ISSN: 0929-8665

β Pore-forming Protein-based Evolutionary Divergence of Gnathostomata from Agnatha

Bhupendra Kumar, Mohd Kashif, Ahad Amer Alsaiari, Mohammad Imran Khan, Abul Kalam, Abrar Ahmad, Rayees Ahmad Lone, Mazen Almehmadi, Shivanand Suresh Dudhagi, Mazin A Zamzami
  • Biochemistry
  • General Medicine
  • Structural Biology


The first vertebrates were jawless fish, or Agnatha, whose evolution diverged into jawed fish, or Gnathostomes, around 550 million years ago.


In this study, we investigated β PFT proteins' evolutionary divergence of lamprey immune protein from Agnatha, reportedly possessing anti-cancer activity, into Dln1 protein from Gnathostomes. Both proteins showed structural and functional divergence, and shared evolutionary origin. Primary, secondary and tertiary sequences were compared to discover functional domains and conserved motifs in order to study the evolution of these two proteins. The structural and functional information relevant to evolutionary divergence was revealed using hydrophobic cluster analysis.


The findings demonstrate that two membrane proteins with only a small degree of sequence identity can have remarkably similar hydropathy profiles, pointing towards conserved and similar global structures. When facing the lipid bilayer or lining the pore lumen, the two proteins' aerolysin domains' corresponding residues displayed a similar and largely conserved pattern. Aerolysin-like proteins from different species can be identified using a fingerprint created by PIPSA analysis of the pore-forming protein.


We were able to fully understand the mechanism of action during pore formation through structural studies of these proteins.

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