ERYTHROCYTE MEMBRANE STRUCTURE

红细胞膜结构

• 批准号: 7418564
• 负责人: PHILIP Stewart LOW
• 金额: $ 45.45万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-07-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7418564
• 关键词: 3-Dimensional; Actins; Affinity; Aldehyde-Lyases; Ankyrins; Architecture; Binding; Binding Proteins; Binding Sites; Biochemical; Biochemistry; Blood flow; Calmodulin; Cell Membrane Structures; Cell membrane; Cellular Morphology; Cytoplasmic Tail; Data; Data Set; Defect; Diagnostic; Enzymes; Equilibrium; Erythrocyte Membrane; Erythrocytes; Fructosediphosphate Aldolase; Glyceraldehyde-3-Phosphate Dehydrogenases; Glycophorin C; Goals; Hematology; Hemoglobin; Hemolytic Anemia; Hemostatic function; Homologous Gene; In Situ; Inositol; Lead; Lesion; Ligands; Lipid Bilayers; Maps; Mechanics; Mediating; Membrane; Membrane Proteins; Membrane Structure and Function; Modeling; Molecular; Molecular Conformation; Morphology; Numbers; Pathway interactions; Peripheral; Phosphorylation; Play; Property; Protein Family; Protein Tyrosine Kinase; Proteins; Regulation; Regulatory Pathway; Role; Shapes; Site; Skeleton; Spectrin; Stimulus; Structural Models; Structure; System; Testing; Text; base; casein kinase I; citrate carrier; dimer; diphosphoglycerate; human SYK protein; improved; neuronal cell body; polypeptide; protein 4.1; src Homology Region 2 Domain

The erythrocyte membrane is depicted in virtually every modern biochemistry text as a model of a plasma membrane, because i) its membrane architecture is comparatively simple, and ii) its protein components or their homologues are present in virtually every cell of the body. The structure of the red blood cell membrane (RBCM) is also of relevance to hematology, because defects in its structure lead to hemolytic anemias, abnormalities in blood flow, and problems in hemostasis. Critical to the structure and function of the RBCM are the two bridges that connect the lipid bilayer to the underlying spectrin-based membrane skeleton; i.e.the band 3-ankyrin-spectrin bridge and the glycophorin C-protein,^.l- spectrin/actin bridge. Defects in either of these bridges lead to altered cell morphology and unwanted membrane fragility. The overriding objective of this proposal is to characterize the structure and regulation of these two bridges. Specifically, we will finish the crystallographic structure determination of the cytoplasmic domain of band 3 (cdb3), the most prominent anchor of the spectrin-based skeleton at the membrane (aim 1). Because cdb3 also binds protein 4.1,protein 4.2,several glycolytic enzymes, hemoglobin, hemichromes, and the protein tyrosine kinase p72syk at defined sequences, this structure determination should greatly expand our understanding of this center of membrane organization. Since crystals of the band 3 binding domain of ankyrin are now available, its crystallographic structure will also be solved. A second aim will focus on characterizing the regulation of the band 3-ankyrin-spectrin bridge. Current data indicate that this regulation is executed either via phosphorylation of band 3 or modulation of the tetramer<->dimer equilibrium of band 3. The effectors that initiate both of the above regulatory changes will be examined in detail. The final specific aim (aim 3) will evaluate the regulation of the glycophorin C-protein 4.1-spectrin/actin bridge. Preliminary data suggest that inositol-l,4,5-trisphosphate (IPs), calmodulin, and 2,3-diphosphoglycerate all play prominent roles in this regulation. These possibilities will be tested in both purified biochemical systems and in situ. As a consequence of these studies, a more thorough understanding of the factors that regulate RBC shape and mechanical stability should ensue.

在几乎所有的现代生物化学教科书中，红细胞膜都被描述为质膜的模型，