3f59
Crystal structure of ZU5-ANK, the spectrin binding region of human erythroid ankyrin
Structural highlights
DiseaseANK1_HUMAN Defects in ANK1 are a cause of spherocytosis type 1 (SPH1) [MIM:182900; also called hereditary spherocytosis type 1 (HS1). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Inheritance can be autosomal dominant or recessive.[1] [2] FunctionANK1_HUMAN Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions.[3] Isoform Mu17 together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils.[4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAs key components of the erythrocyte membrane skeleton, spectrin and ankyrin specifically interact to tether the spectrin cytoskeleton to the cell membrane. The structure of the spectrin binding domain of ankyrin and the ankyrin binding domain of spectrin have been solved to elucidate the structural basis for ankyrin-spectrin recognition. The structure of repeats 14 and 15 of spectrin shows that these repeats are similar to all other spectrin repeats. One feature that could account for the preference of ankyrin for these repeats is the presence of a conserved, negatively charged patch on one side of repeat 14. The structure of the ankyrin ZU5 domain shows a novel structure containing a beta core. The structure reveals that the canonical ZU5 consensus sequence is likely to be missing an important region that codes for a beta strand that forms part of the core of the domain. In addition, a positively charged region is suggestive of a binding surface for the negatively charged spectrin repeat 14. Previously reported mutants of ankyrin that map to this region lie mostly on the surface of the protein, although at least one is likely to be part of the core. Structures of the spectrin-ankyrin interaction binding domains.,Ipsaro JJ, Huang L, Mondragon A Blood. 2009 May 28;113(22):5385-93. Epub 2009 Jan 13. PMID:19141864[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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