Membrane protein interactions in sickle red blood cells: evidence of abnormal protein 3 function
| Autor: | Jill F. Falcone, Orah S. Platt |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
chemistry.chemical_classification
Immunology EPB41 Tyrosine phosphorylation macromolecular substances Cell Biology Hematology Plasma protein binding Biology medicine.disease Biochemistry Sickle cell anemia Cell biology chemistry.chemical_compound Membrane protein chemistry ANK1 medicine Ankyrin Spectrin |
| Zdroj: | Blood. 86:1992-1998 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v86.5.1992.bloodjournal8651992 |
| Popis: | The pattern of membrane abnormalities in sickle red blood cells suggests that sickle hemoglobin damages membrane proteins. We have previously shown a functional defect in sickle ankyrin, poor spectrin- binding ability. Here we examine the other major binding interactions of sickle membrane proteins including spectrin self-association, binding of ankyrin and protein 4.1 to protein 3, and the formation of the spectrin-actin-protein 4.1 complex. We found that sickle spectrin was normal in self-association and ability to participate in the spectrin-actin-protein 4.1 complex. Sickle protein 4.1 bound normally to protein 3 and formed normal complexes with actin and spectrin, even when sickle spectrin was used. The only major abnormality we found was a reduced ability of sickle protein 3 to bind ankyrin. This functional defect could not be explained experimentally on the basis of cysteine modification or enhanced tyrosine phosphorylation. We conclude that damage of sickle membrane proteins is not a diffuse scattershot process, but is largely confined to regions near membrane-associated hemoglobin, the spectrin-binding domain of ankyrin and the ankyrin- binding domain of protein 3. The mechanism and consequences of this damage continues to be investigated. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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