How our cells (nearly) perfected making nanobots

Stanley Prusiner discovered prions—infectious misfolded proteins—earning the 1997 Nobel Prize. Researchers study Alzheimer’s, Parkinson’s, Huntington’s, and ALS involving protein aggregation. Cystic fibrosis results from CFTR misfolding and premature degradation. Sickle cell disease arises from single glutamine-to-lysine mutation causing hemoglobin misfolding and aggregation.

Venkatraman Ramakrishnan, Thomas Steitz, and Ada Yonath determined ribosome structure earning the 2009 Nobel Prize in Chemistry. Structural studies revealed the exit tunnel through which nascent proteins emerge. Biochemists study co-translational folding showing proteins begin folding before synthesis completes.

Ferruccio Ritossa discovered heat shock response in 1962 observing chromosomal puffing in heat-stressed Drosophila. Alfred Tissières identified heat shock proteins. Susan Lindquist studied HSP90’s roles in evolution and disease. Cell biologists recognize heat shock as universal stress response conserved from bacteria to humans.

Ulrich Hartl and Franz-Ulrich Hartl characterized HSP70 and HSP40 chaperone mechanisms. Sue Lindquist studied chaperone roles in disease and evolution. Heat shock protein discovery by Ferruccio Ritossa in 1962 revealed stress-induced protein expression. Cell biologists recognize chaperones as essential protein homeostasis machinery preventing aggregation and assisting folding.

Arthur Horwich and Ulrich Hartl elucidated GroEL/GroES mechanism revealing how chaperonins provide isolated folding chambers. Hugh Pelham discovered eukaryotic chaperonin TRiC/CCT. Structural biologists visualized chaperonin conformational cycles showing ATP-driven chamber opening and closing. Biochemists estimate 10-15% of E. coli proteins require chaperonin assistance.

Avram Hershko, Aaron Ciechanover, and Irwin Rose discovered ubiquitin-mediated protein degradation earning the 2004 Nobel Prize. Structural biologists determined proteasome architecture revealing how substrates enter catalytic chambers. Cell biologists study ubiquitin signaling regulating cell cycle, signal transduction, and quality control.