Molecular Mapping of the Active Site of an Aging Antigen
An aging antigen, senescent cell antigen, resides on the 911 amino acid membrane protein band 3. It marks cells for removal by initiating specific IgG autoantibody binding (1–22). This appears to be a general physiologic process for removing senescent and damaged cells in mammals and other vertebrates (4). Although the initial studies were done using human erythrocytes as a model, senescent cell antigen occurs on all cells examined (4). The aging antigen itself is generated by the degradation of an important structural and transport membrane molecule, protein band 3 (5). Besides its role in the removal of senescent and damaged cells, senescent cell antigen also appears to be involved in the removal of erythrocytes in clinical hemolytic anemias (7,8), and the removal of malaria-infected erythrocytes (23,24). Oxidation generates senescent cell antigen in situ (6). Neither cross-linking nor hemoglobin appear to play a role. Although storage is the only in vitro model that mimics cellular aging in situ, we have discovered three alterations/mutations of band 3 that permit insight into aging in situ. One mutation with an addition to band 3 has normal or decelerated red cell aging. In contrast, another band 3 alteration with a suspected deletion or substitution that renders band 3 more susceptible to proteolysis, shows accelerated aging. The third alteration which is also more susceptible to proteolysis is associated with neurologic defects.
KeywordsHuman Erythrocyte Senescent Cell Anion Transport Antigenic Site Transport Domain
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