Spectrin: Structure, function and disease (1)
Spectrin is a cytoskeletal protein that was first discovered in erythrocytes and is important for maintaining the stability, structure, and shape of the cell membrane. There are two and five subunits of human spectrin (I, II, I, II, III, IV, and V). The molecular weights of the and subunits are 280 and 246 kD, respectively. The amino acid sequences of spectrin and subunits share approximately 30% similarity, and the subunits are associate side-to-side.
To explain the structure and function of spectrin, a miniature spectrin that simulates the structural and functional properties of whole spectrin dimers and tetramers were illustrated.
Except for the resolved spectrin repeat fragments, the crys- tal and NMR structures of the domains interacting with other proteins have also been resolved, including actin-binding and pleckstrin homology domains.
By interacting with various membrane proteins, spectrin provides a versatile platform for other proteins, making it a multi-functional protein.
Spectrin is involved in the tumor growth factor (TGF)-β/SMAD signaling pathway as a SMAD3/4 adaptor. The link between spectrin and the (TGF)-β/SMAD signaling pathway was first indicated by the molecular cloning of a cDNA (elf1) encoding a β spectrin homolog designated embryonic liver fodrin 1 (ELF1).
The absence of cytoskeletal components can generate weak and fragile cells that manifest clinically as types of hemolytic anemia, including hereditary elliptocytosis (HE) and HS. All HE cases involve defects in the spectrin-actin-4.1R complex. All HS have one common feature: the loss of cell membrane surface area causes a spherical phenotype and an increased level of erythrocyte osmotic fragility. Spectrin cannot be anchored to the cell membrane, and the destruction of membrane protein interactions such as that between spectrin and ankyrin, ankyrin and band3, band3 and protein 4.2, is the main mechanism that causes HS. Spectrin represents 2%-3% of the total protein content of the brain and is located in neuronal synapses related to the connection between neurons in the presynaptic membrane and synaptic vesicles. Spectrin may also provide host binding sites for entero- hemorrhagic Escherichia coli (EHEC) that causes gastrointestinal disease.