Reconciling crystallography and mutagenesis: a synthetic approach to the creation of a comprehensive model for proton pumping by bacteriorhodopsin

As a result of the number of new high-resolution structures of the pigment and some of its photointermediates, a realistic model for the functioning of bacteriorhodopsin seems to be finally emerging. However, lack of structural information for some of the key functional states, and contradictions between some published structural models, argue for the use of the synthetic approach, one that includes use of data from both crystallographic and mutagenesis studies. The role of mutagenesis in this synthetic approach falls into two categories. First, to provide additional structural information, and second, to test the predictions of structural models by studying mutant phenotypes. This review urges critical comparisons of the structural and mutagenesis data, as there are problems with their selective and indiscriminate use.