Tracing a protein's folding pathway over evolutionary time using ancestral sequence reconstruction and hydrogen exchange.

ABSTRACT: The conformations populated during protein folding have been studied for decades; yet, their evolutionary importance remains largely unexplored. Ancestral sequence reconstruction allows access to proteins across evolutionary time, and new methods such as pulsed-labeling hydrogen exchange coupled with mass spectrometry allow determination of folding intermediate structures at near amino-acid resolution. Here, we combine these techniques to monitor the folding of the ribonuclease H family along the evolutionary lineages of T. thermophilus and E. coli RNase H. All homologs and ancestral proteins studied populate a similar folding intermediate despite being separated by billions of years of evolution. Even though this conformation is conserved, the pathway leading to it has diver

SUBMITTER: Lim SA 

PROVIDER: S-EPMC6158009 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature