Author:
Machnicka Beata,Czogalla Aleksander,M. Bogusławska Dżamila,Stasiak Piotr,Sikorski Aleksander F.
Abstract
AbstractPreviously, we reported a new missense mutation in theANK1gene correlated with the HS phenotype. This mutation, resulting in L1340P substitution (HGMD CM149731), likely leads to the changes in the conformation of the ankyrin ZZUD domain important for ankyrin binding to spectrin. In this report, we have shown the molecular and physiological effects of this mutation. First, we assessed the binding activity of human β-spectrin to the mutated ZZUDL1340P domain of ankyrin using two different experimental approaches – the study of association and dissociation responses of spectrin ankyrin binding domain and sedimentation assay. In addition, we demonstrated changes in morphology caused by the overexpressed ankyrin ZZUD domain in human cell models. Our results prove the key role of L1340 aa residue in the UPA domain for the correct alignment of the ZZUD domain of ankyrin, which results in binding the latter with spectrin within the erythrocyte membrane. Replacing the L1340 with a proline residue disrupts the spectrin binding activity of ankyrin.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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