3 QUATERNARY STRUCTURES FOR A SINGLE PROTEIN

The structure of a multisubunit protein (immunoglobulin light chain) w as solved in three crystal forms, differing only in the solvent of cry stallization. The three structures were obtained at high ionic strengt h and low pH, high ionic strength and high pH, and low ionic strength and neutral pH. The three resulting ''snapshots'' of possible structur es show that their variable-domain interactions differ, reflecting the ir stabilities under specific solvent conditions. In the three crystal forms, the variable domains had different rotational and translationa l relationships, whereas no alteration of the constant domains was fou nd. The critical residues involved in the observed effect of the solve nt are tryptophans and histidines located between the two variable dom ains in the dimeric structure. Tryptophan residues are commonly found in interfaces between proteins and their subunits, and histidines have been implicated in pH-dependent conformation changes. The quaternary structure observed for a multisubunit protein or protein complex in a crystal may be influenced by the interactions of the constituents with in the molecule or complex and/or by crystal packing interactions. The comparison of buried surface areas and hydrogen bonds between the dom ains forming the molecule and between the molecules forming the crysta ls suggest that, for this system, the interactions within the molecule are most likely the determining factors.