Aortic disease-linked mutations reveal unexpected convergent allosteric mechanisms of protein kinase G misregulation.

doi:10.1126/sciadv.aeg1640

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Article

Aortic disease-linked mutations reveal unexpected convergent allosteric mechanisms of protein kinase G misregulation.

Science advances - 4 Sept 2026

Martinez Pomier Karla, Jahn Leopold, VanSchouwen Bryan, Mohamed Hebatallah, Akimoto Madoka, Jung Sun Woo, Bertinetti Daniela, Mehringer Johannes, Della Libera Leonardo, Cuello Friederike, Herberg Friedrich W, Melacini Giuseppe

Abstract excerpt

Thoracic aortic aneurysms and dissections (TAAD) are life-threatening conditions linked to gain-of-function mutations in cGMP-dependent protein kinase I (PKG I), a central regulator of vascular smooth muscle signaling. Among these, substitutions at Val234 have been associated with kinase overactivation and early-onset disease, despite this residue being distal from the active site and cGMP binding regions. Using...

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Topics

Allosteric Regulation
Humans
Mutation
Cyclic GMP-Dependent Protein Kinase Type I
Cyclic GMP

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Molecular Dynamics Simulation

Signal Transduction

Aortic Aneurysm, Thoracic

Dissection, Thoracic Aorta

Cyclic GMP-Dependent Protein Kinases

Protein Binding

Protein Conformation

Catalytic Domain

Aortic Dissection

Source

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Identifiers

PMID: 42685200
DOI: 10.1126/sciadv.aeg1640
PMCID: PMC13537252

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