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Updated: May 20, 2026

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
Microenvironmental pH and host-pathogen co-evolution potentially influence the structural architecture of junctional
Taner Karagöl1, Alper Karagöl2
1Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey. karagol.mahmuttaner@ogr.iu.edu.tr.
Junctional adhesion molecules (JAMs) proteins evolved diverse functions by adapting to changing pH environments. Isoelectric point divergence correlates with residue evolution and pH-dependent dynamics, offering insights into protein adaptation.
Area of Science:
- Evolutionary biology
- Molecular biology
- Biochemistry
Background:
- Junctional adhesion molecules (JAMs) are crucial for immune regulation and cell adhesion.
- Understanding protein adaptation to physiological microenvironments is a key biological challenge.
Purpose of the Study:
- Investigate the evolutionary and structural dynamics of JAM paralogs across mammalian taxa.
- Explore how isoelectric points (pI) and pH influence JAM protein diversification.
Main Methods:
- Phylogenetic modeling
- Partial correlation analysis
- Network topology analysis
- Evolutionary molecular dynamics simulations across a pH gradient
- AlphaMissense profiling
Main Results:
- JAM-B identified as a central node in the conservation network with Lys and Cys as key residues.
- Episodic selection bursts observed in 17-26% of mammalian lineages, particularly at JAM-A's viral entry interface.
- Acidic to basic mutations showed lower pathogenicity scores; pH-dependent dynamics identified for JAM-A and JAM-C.
Conclusions:
- Isoelectric divergence is linked to residue evolution and pH-specific structural dynamics in JAMs.
- The study provides a framework for understanding paralog diversification and therapeutic modulation of pH-sensitive adhesion.
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