SIGNAL-TRANSDUCTION VERSUS BUFFERING ACTIVITY IN CA2-BINDING PROTEINS()

The three-dimensional structure of calbindin D-9k in the absence of Ca 2+ has been determined using NMR spectroscopy in solution, allowing th e first direct analysis of the consequences of Ca2+ binding for a memb er of the calmodulin superfamily of proteins. The overall response in calbindin D-9k is much attenuated relative to the current model for ca lmodulin and troponin C. These results demonstrate a novel mechanism f or modulating the conformational response to Ca2+-binding in calmoduli n superfamily proteins and provide insights into how their Ca2+-bindin g domains can be fine-tuned to remain essentially intact or respond st rongly to ion binding, in relation to their functional requirements.