INTRAGENIC SUPPRESSORS OF DICTYOSTELIUM MYOSIN G680 MUTANTS DEMARCATEDISCRETE STRUCTURAL ELEMENTS - IMPLICATIONS FOR CONFORMATIONAL STATESOF THE MOTOR

We are using intragenic suppression to generate inferences about curre ntly inaccessible conformations of the molecular motor myosin. We iden tified 19 unique suppressors of Dictyostelium G680A and G680V mutants and find that they are structurally and chemically restricted, suggest ive of specific, compensatory mechanisms of action. Suppressors cluste r in two adjacent elements of the myosin structure, one of which is do minated by substitutions that increase the volume of hydrophobic resid ues. The suppressors outline a general model for the mechanism of supp ression of the G680A and G680V alterations. Secondary phenotypes confe rred by suppressors independent of the G680 changes demonstrate that t hey will be useful substrates for biochemical and genetic characteriza tion.