Phospholipid binding by proteins of the spectrin family: a comparative study

Abstract

Erythroid and neuronal spectrin (fodrin) are both known to interact strongly with the aminophospholipids that occur in the inner leaflet of plasma membranes. In erythroid spectrin the positions of the binding sites within the constituent (αI and βI) polypeptide chains have been defined, and also the importance of the lipid interaction in regulating the properties of the membrane. Here we report the locations of the corresponding binding sites in the αII and βII chains that make up the fodrin molecule. Of the 10 lipid-binding repeats in the erythroid spectrin chains 5 are conserved in fodrin; one cluster of 3 consecutive structural repeating units in αI erythroid spectrin (repeats 8–10) is displaced by one repeat in αII fodrin (repeats 9–11). Fodrin also contains one binding site at the N-terminus of the αII chain, not present in the erythroid protein. The regions of the two spectrins containing equivalent lipid-binding sites show a much higher degree of sequence identity than corresponding repeats that do not share this property. The evolutionary conservation of the distribution of a large proportion of strong lipid-binding sites in the polypeptide chains of these two proteins of disparate character argues for a specific function of fodrin-phospholipid interactions in the neuron.