John Christodoulou

1 month ago | science.org | Barbara von Hippel |Jinke Chang |Christopher A. Waudby |Elena Emili |Sarah M. Lowen |Alistair M. Jagger | +6 more

AbstractSerpins, protease inhibitors whose regulated conformational instability renders them susceptible to mutations that cause misfolding, represent a system for the study of non-amyloid protein aggregation. The E342K “Z” variant of α-1-antitrypsin (AAT) undergoes oligomeric self-assembly into polymer chains that are associated with liver and lung pathologies in AAT deficiency.

Oct 16, 2024 | nature.com | Nicole J Lake |Kaiyue Ma |Stephanie L. Battle |Kenneth Ng |Alison G. Compton |John Christodoulou | +4 more

AbstractMitochondrial DNA (mtDNA) has an important yet often overlooked role in health and disease. Constraint models quantify the removal of deleterious variation from the population by selection and represent powerful tools for identifying genetic variation that underlies human phenotypes1,2,3,4. However, nuclear constraint models are not applicable to mtDNA, owing to its distinct features.