Solution structural studies on human erythrocyte alpha-spectrin tetramerization site.
We have determined the solution NMR structure of a recombinant peptide that consists of the first 156 residues of erythroid alpha-spectrin. The first 20 residues preceding the first helix (helix C') are in a disordered conformation. The subsequent three helices (helices A1, B1, and C1) form a triple helical bundle structural domain that is similar, but not identical, to previously published structures for spectrin from Drosophila and chicken brain. Paramagnetic spin label-induced NMR resonance broadening shows that helix C', the partial domain involved in alpha- and beta-spectrin association, exhibits little interaction with the structural domain. Surprisingly, helix C' is connected to helix A1 of the structural domain by a segment of 7 residues (the junction region) that exhibits a flexible disordered conformation, in contrast to the predicted rigid helical structure. We suggest that the flexibility of this particular junction region may play an important role in modulating the association affinity of alpha- and beta-spectrin at the tetramerization site of different isoforms, such as erythroid spectrin and brain spectrin. These findings may provide insight for explaining various physiological and pathological conditions that are a consequence of varying alpha- and beta-subunit self-association affinities in their formation of the various spectrin tetramers.
Park
Sunghyouk
S
Center for Pharmaceutical Biotechnology, University of Illinois, 900 S. Ashland, Chicago, IL 60607, USA.
Caffrey
Michael S
MS
Johnson
Michael E
ME
Fung
Leslie W-M
LW
D000818:Animals; D019281:Dimerization; D004330:Drosophila; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D020033:Protein Isoforms; D013049:Spectrin / Q000737:chemistry* / Q000378:metabolism; D013113:Spin Labels
D010455:Peptides; D020033:Protein Isoforms; D013113:Spin Labels; D013049:Spectrin