Joseph C. Genereux

We are excited to share this special issue dedicated to Jeffery Kelly, commemorating his 2023 Wolf Prize in Chemistry. This award recognizes his pioneering research accomplishments, which have dramatically changed our fundamental understanding of how proteins (mis)fold in vitro and in vivo while at the same time leveraging those discoveries to change the lives of patients across the globe.

Introduction Click to copy section linkSection link copied! The vast majority of proteins in the human body are synthesized, folded, and degraded back into amino acids within 24 h to 10 days. (1−3) However, long-lived proteins (LLPs) are a subset of the proteome that have half-lives ranging from weeks to decades.

Abstract Spontaneous chemical modifications in long-lived proteins can potentially change protein structure in ways that impact proteostasis and cellular health. For example, isomerization of aspartic acid interferes with protein turnover and is anticorrelated with cognitive acuity in Alzheimer's disease. However, few isomerization rates have been determined for Asp residues in intact proteins.