Origins of protein folding

CREATED: 200804010118 Speaker: Andrei Lupas, Max Planck Insitute of Developmental Biology

Facts about protein foldin

• needs to assumed a defined 3D structure
• randomly peptide chains do not fold, ~ 1 in $10^{10}$
• RNA (both as templates and active agent) preceded proteins
• relatively few stable structures
• most proteins preserve their structure but not their sequence

Main hypothesis

• decomposition of proteins into main supersecondary structures
• folded proteins evolved by fusion and recombination from an ancestral set of peptides, which emerged in the context of RNA-dependent replication and catalysis
• analogous to the way words evolve in languages
• functional drift

Goal

• identify library of supersecondary structures
• how complex structures evolved

Recognizing remote homology

• HHsearch makes use of HMM incorporating both the sequence and secondary structure information
• toolkit.tuebingen.mpg.de

Galaxy of folds