The common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation.

ABSTRACT: Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are common disorders of erythrocyte shape primarily because of mutations in spectrin. The most common HE/HPP mutations are located distant from the critical αβ-spectrin tetramerization site, yet still interfere with formation of spectrin tetramers and destabilize the membrane by unknown mechanisms. To address this question, we studied the common HE-associated mutation, αL260P, in the context of a fully functional mini-spectrin. The mutation exhibited wild-type tetramer binding in univalent binding assays, but reduced binding affinity in bivalent-binding assays. Biophysical analyses demonstrated the mutation-containing domain was only modestly structurally destabilized and helical content was not significantly changed. G

SUBMITTER: Harper SL 

PROVIDER: S-EPMC3811177 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature