HYDROGEN-EXCHANGE - THE MODERN LEGACY OF LINDERSTROM-LANG

This discussion, prepared for the Protein Society's symposium honoring the 100th anniversary of Kaj Linderstrom-Lang, shows how hydrogen exc hange approaches initially conceived and implemented by Lang and his c olleagues some 50 years ago are contributing to current progress in st ructural biology. Examples are chosen from the active protein folding field. Hydrogen exchange methods now make it possible to define the st ructure of protein folding intermediates in various contexts: as tenuo us molten globule forms at equilibrium under destabilizing conditions, in kinetic intermediates that exist for less than one second, and as infinitesimally populated excited state forms under native conditions. More generally, similar methods now find broad application in studies of protein structure, energetics, and interactions. This article cons iders the rise of these capabilities from their inception at the Carls berg Labs to their contemporary role as a significant tool of modem st ructural biology.