Description:
<jats:title>Significance</jats:title>
<jats:p>High pressure unfolds proteins due to a larger volume of the native state compared with the unfolded state, but the molecular origin of the volume changes is still under debate. Virtually no information is available on volume changes associated with secondary structure formation. We reveal that α-helices become stabilized with increasing pressure, which explains the commonly observed residual helical structure in pressure-unfolded proteins. The transition state for the helix–coil transition has a larger volume than both the helical and the coil state. Thus, addition or removal of a helical residue proceeds through a transitory high-energy state with a large volume, possibly due to the presence of unsatisfied hydrogen bonds, although steric effects may also be involved.</jats:p>