Abstract
The α and β subunits comprising the hexameric assembly of F1-ATPase share a high degree of structural identity, though low primary identity. Each subunit binds nucleotide in similar pockets, yet only β subunits are catalytically active. Why? We re-examine their internal symmetry axes and observe interesting differences. Dividing each chain into an N-terminal head region, a C-terminal foot region, and a central torso, we observe (1) that while the foot and head regions in all chains obtain high and similar mobility, the torsos obtain different mobility profiles, with the β subunits exhibiting a higher motility compared to the α subunits, a trend supported by the crystallographic B-factors. The β subunits have greater torso mobility by having fewer distributed, nonlocal packing interactions providing a spacious and soft connectivity and offsetting the resultant softness with local stiffness elements, including an additional β sheet. (2) A loop near the nucleotide binding-domain of the β subunits, absent in the α subunits, swings to create a large variation in the occlusion of the nucleotide binding region. (3) A combination of the softest three eigenmodes significantly reduces the root mean square difference between the open and closed conformations of the β subunits. (4) Comparisons of computed and observed crystallographic B-factors suggest a suppression of a particular symmetry axis in an α subunit. (5) Unexpectedly, the soft intra-monomer oscillations pertain to distortions that do not create inter-monomer steric clashes in the assembly, suggesting that structural optimization of the assembly evolved at all levels of complexity.
Highlights
We examine the question: why do b subunits readily hydrolyze ATP and exchange the HOH generated with medium water, while the a subunits neither hydrolyze nor exchange ATP with solvent nucleotides? Xu and coworkers1 point out that while the nucleotide-binding sites in a and b subunits are closely conserved, one carboxylate of residue b-Glu 188 is replaced by a-Gln 208, eliminating a likely catalytic base in the a subunits
We examined the reasons why two proteins with nearly identical topology and fold but with different primary sequences behave very differently within the same assembly: one as a structural protein and the other as an enzyme
Active site motility is enabled by relatively low nonbonded interactions (NBIs) or packing densities in critical junctures that create sufficient space to permit opening and closing movements
Summary
In F1-ATPase the three a subunits (SUA) and three b subunits (SUB) alternate as the segments of an orange to create a cap-like structure with an outer diameter of around 100 Aand a central channel about 20 Aacross. This central channel, marking the axis of pseudosymmetry, contains a pair of coiled-coil a helices formed by the N and C terminal domains of the c subunit. The remainder of the c chain as well as the smaller d and chains forms a globular arrangement attached to the central a helices like the head of a golf club to its shaft
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have