Mechanisms of cytoskeletal regulation: functional and antigenic diversity in human erythrocyte and brain beta spectrin.
A study of human erythrocyte and brain spectrin with particular emphasis on the beta subunits revealed a structural homology but functional dissimilarity between these two molecules. Six monoclonal antibodies raised to human erythrocyte beta spectrin identify three of the four proteolytically defined domains of erythrocyte beta spectrin. Five of these monoclonal antibodies cross-react with human brain spectrin. None of a previously identified set of alpha erythrocyte spectrin monoclonal antibodies [Yurchenco et al: J Biol Chem 257:9102, 1982] reacted with brain spectrin. A domain map generated by limited tryptic digestion shows that brain spectrin is composed of proteolytically resistant domains analogous to erythrocyte spectrin, but the brain protein is more basic. The binding of brain spectrin to erythrocyte ankyrin, both in solution and on erythrocyte IOVs, yielded an association constant approximately 100 time weaker than for erythrocyte spectrin. The binding of azido-calmodulin under native conditions was specific for the erythrocyte beta subunit but was not calcium dependent. In contrast, azido-calmodulin bound only to the alpha subunit of brain spectrin in a calcium-dependent manner. The similarity of structure but modified functional characteristics of the brain and erythrocyte beta spectrins suggest that these proteins serve different cellular roles.
A S
AS
Harris
J P
JP
Anderson
P D
PD
Yurchenco
L A
LA
Green
K J
KJ
Ainger
J S
JS
Morrow
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D017487:Ankyrins; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001665:Binding Sites; D001923:Brain Chemistry; D002147:Calmodulin / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology*; D000939:Epitopes / Q000276:immunology*; D004912:Erythrocytes / Q000032:analysis*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D013049:Spectrin / Q000276:immunology / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D000596:Amino Acids; D017487:Ankyrins; D000911:Antibodies, Monoclonal; D002147:Calmodulin; D000939:Epitopes; D008565:Membrane Proteins; D010446:Peptide Fragments; D013049:Spectrin; D014357:Trypsin