PMC

Each PBGS monomer consists of an α₈β₈-barrel domain, the center of which holds the enzyme active site, and an N-terminal arm domain. Some PBGS also contain N-terminal and C-terminal extensions, not shown here. The top pathway (left to right) shows octamer dissociating to hugging dimers, a conformational change to detached dimers, and assembly to the hexamer. The hugging dimer is the asymmetric unit of many PBGS crystal structures; the N-terminal arm of one subunit “hugs” the α₈β₈-barrel of the neighboring subunit. The detached dimer, which does not have the hugging interaction, is the asymmetric unit of the crystal structure of the hexameric human PBGS variant, F12L []. The location of one hugging and one detached dimer in the octamer and hexamer respectively are shown using dashed ovals. The bottom pathway shows octamer dissociating to pro-octamer dimers, a conformational change to pro-hexamer dimers, and assembly to the hexamer. The positions of one pro-octamer and one pro-hexamer dimer in the octamer and hexamer respectively are shown using dotted ovals. Conformations that support octamer assembly are shown in shades of red; conformations that support hexamer assembly are shown in shades of blue. Light and dark shades are used for contrast in these homo-oligomeric assemblies.

a) A three dimensional dice analogy is used to illustrate how a die that can morph between a cube and a tetrahedron leads to the assembly of a tetramer and a pentamer respectively. In this case, the common rule of subunit assembly is that “four dots” associate with “one dot”. b) The morpheein model of allosteric regulation is illustrated using a two dimensional geometric analogy. A subunit whose conformation is that of a pie wedge (blue) is in equilibrium with a rectangular conformation (pink). The common rule of subunit assembly is that a “dashed line” associates with a “thick line” such that the pie wedge assembles into a circular trimer and the rectangle assembles into a square tetramer. An allosteric regulator, illustrated as a yellow wedge, is shaped to bind preferentially to elements of the trimer. Regulator binding stablizes the blue components of the equilibrium and draws the equilibrium in the direction of the trimer.