Spectrin self-association site: characterization and study of beta-spectrin mutations associated with hereditary elliptocytosis
| Autor: | C Craescu, S Pedroni, Marie-Christine Lecomte, H. Gautero, Didier Dhermy, Gaël Nicolas, Catherine Fournier |
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| Přispěvatelé: | NICOLAS, Gaël, Génétique et pathologie moléculaires de l'hématopoïèse, Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique moléculaire, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
MESH: Mutation
Erythrocytes Dimer Hereditary elliptocytosis MESH: Protein Structure Secondary MESH: Elliptocytosis Hereditary medicine.disease_cause hereditary elliptocytosis Biochemistry Protein Structure Secondary MESH: Circular Dichroism MESH: Recombinant Proteins chemistry.chemical_compound [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology medicine MESH: Protein Binding Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Spectrin MESH: Peptide Fragments Beta (finance) Molecular Biology Mutation MESH: Humans Binding Sites Chemistry MESH: Erythrocytes Circular Dichroism Elliptocytosis Hereditary MESH: Spectrin Cell Biology medicine.disease Haemolysis anemia Peptide Fragments Recombinant Proteins MESH: Mutagenesis Site-Directed MESH: Binding Sites MESH: Dimerization Helix Biophysics Mutagenesis Site-Directed Dimerization Alpha chain Research Article Protein Binding |
| Zdroj: | Biochemical Journal Biochemical Journal, Portland Press, 1998, 332 ( Pt 1), pp.81-9 ResearcherID |
| ISSN: | 0264-6021 1470-8728 |
| Popis: | International audience; Most of hereditary elliptocytosis (HE) cases are related to a spectrin dimer (SpD) self-association defect. The severity of haemolysis is correlated with the extent of the SpD self-association defect, which itself depends on the location of the mutation regarding the tetramerization site. This site is presumed to involve the first C helix of the alpha chain and the last two helices, A and B, of the beta chain to reconstitute a triple helical structure (A, B and C), as observed along spectrin. Using recombinant peptides, we demonstrated that the first C helix of the alpha chain and the last two helices of the beta chain alone are not sufficient to establish interactions, which only occurred when a complete triple-helical repeat was added to each partner. One adjacent repeat is necessary to stabilize the conformation of both N- and C-terminal structures directly involved in the interaction site and is sufficient to generate a binding affinity similar to that observed in the native molecule. Producing peptides carrying a betaHE mutation, we reproduced the tetramerization defect as observed in patients. Therefore, the betaW2024R and betaW2061R mutations, which replace the invariant tryptophan and a residue located in the hydrophobic core, respectively, affect alpha-beta interactions considerably. In contrast, the betaA2013V mutation, which modifies a residue located outside any presumed interacting regions, has a minor effect on the interaction. |
| Databáze: | OpenAIRE |
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