Calcium Binding Proteins and Their Natural Classiﬁcation
Calcium-binding proteins comprise a large family of proteins that can be subdivided into two subfamilies based on their molecular organisation. A large number of these proteins have been identiﬁed and characterised, and their physiological functions have been investigated (Tables 2 and 3). The subfamily of CBPs, referred to here as non-EF-hand CBPs, binds to certain phospholipids in a calcium-dependent fashion (Heizmann and Hunziker, 1990). They do not possess the characteristic feature of the other subfamily, popularly described as the EF-hand CBPs. The EF-hand protein subfamily in turn can be divided into two groups (Da Silva and Reinach, 1991). The members of one group function as Ca
sensor proteins. These are inactive at calcium concentrations in the low range of 10
. They are activated into playing their regulatory role when the Ca
concentration increases to around 10
. The second group comprises EF-hand proteins that are mainly concerned with calcium buffering and transport. Calcium ions function as second messengers
in many pathways of cellular response. The translation of the calcium signal into biological function is mediated by CBPs that occur ubiquitously in intracellular locations as well as in the extracellular matrix. In order to be able to mediate the transduction of calcium signalling into cellular responses, CBPs need to recognise and interact with downstream target proteins. The binding of Ca
to CBPs produces conformational changes in these molecules and these changes appear to endow the CBPs with the ability to recognise and interact with their target molecules. This is discussed in greater detail in a later section.