We
often encounter a case where two proteins, whose amino-acid
sequences are similar, are quite different with regard to the thermostability.
As a striking example, we consider the two seven-transmembrane proteins:
recently discovered Rubrobacter xylanophilus rhodopsin (RxR) and long-known bacteriorhodopsin from Halobacterium salinarum (HsBR). They commonly function
as a light-driven proton pump across the membrane. Though their sequence
similarity and identity are ā¼71 and ā¼45%, respectively,
RxR is much more thermostable than HsBR. In this study, we solve the
three-dimensional structure of RxR using X-ray crystallography and
find that the backbone structures of RxR and HsBR are surprisingly
similar to each other: The root-mean-square deviation for the two
structures calculated using the backbone CĪ± atoms
of the seven helices is only 0.86 Ć
, which makes the large stability
difference more puzzling. We calculate the thermostability measure
and its energetic and entropic components for RxR and HsBR using our
recently developed statistical-mechanical theory. The same type of
calculation is independently performed for the portions playing essential
roles in the proton-pumping function, helices 3 and 7, and their structural
properties are related to the probable roles of water molecules in
the proton-transporting mechanism. We succeed in elucidating how RxR
realizes its exceptionally high stability with the original function
being retained. This study provides an important first step toward
the establishment of a method correlating microscopic, geometric characteristics
of a protein with its thermodynamic properties and enhancing the thermostability
through amino-acid mutations without vitiating the original function.