CONFORMATIONAL CHANGES IN THE B SUBUNIT OF F1 ATPASE
J.P. Abrahams
Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands
Keywords: Protein structure, conformational change, bioenergtics
Further study of the crystal structure of bovine mitochondrial F1 ATPse revealed several hitherto undiscussed features. The motion within the b subunit during catalysis was described as a hinging motion of two rigid bodies [1]. This was a deliberate simplification as the two domains that move relative to one another also undergo internal distortions. Closer inpection reveals the nature of these distortions and indicates how a cascade of interactions, starting in the g subunit, distort the upper half of the nucleotide binding domain, thus withdrawing catalytically important residues from the active site in the b-E subunit.
Inspection of electron density omit maps calculated form the 2.8 A data [1] indicates the clear presence of elongated density in the phosphate binding site of the empty b-E subunit. It is possible that at this location ATP or ADP is bound, but that the adenine moiety is disordered. The ordering of the adenine moiety in the nucleotide binding conformation of b-DP and b-TP is explained by the sandwich of the purine between aromatic residues of the C-terminal domain.
The conformational transition that ATP synthase undergoes during catalysis requires the disruption and formation of a large number of hydrogen bonds. In the absence of an enthropic term, the transition would therefore be far to slow to be practical. However, it turns out that the C-terminal domain of the nucleotide releasing b-E subunit is less well ordered. It is proposed that the enthropy associated with this disorder forms an important contribution towards the lowering of the free energy of the transition states, thus speeding up catalysis.
Abrahams, J.P., Leslie, A.G.W, Lutter, R. & Walker, J.E. (1994) "Structure at 2.8 A resolution of F1 ATPase from bovine heart mitochondria", Nature 370, 621-628