Ankyrin

The ankyrin repeat motif is one of the most common protein-protein interaction domains. Ankyrin repeats are modules of about 33 amino acids repeated in tandem. They are found in a large number of proteins with diverse cellular functions such as transcriptional regulators, signal transducers, cell-cycle regulators, and cytoskeletal proteins. 

Ankyrin deficiency, amounting to a reduction of approximately 50%, has been found in some patients with the dominant type of HS. A primary defect in ankyrin almost certainly reduces the assembly of spectrin into the membrane skeleton of the red blood cell (Davies and Lux, 1989). 

Proteins closely related to spectrin and ankyrin and many of the associated proteins first identified in erythrocytes also are prevalent in most vertebrate tissues. In these other tissues, spectrin and ankyrin and their associated proteins interact with proteins that may not be expressed in erythrocytes, including ion channel... 

Nelson, W.J. Hammerton, R.W. (1989). A membrane-cytoskeletal complex containing Na, K -AT-Pase, ankyrin, and fodrin in Madin-Darby canine kidney (MDCK cells) Implications for the biogenesis of epithelial cell polarity. J. Cell Biol. 108, 893-902. 

Nelson, W.J. Veshnock, P.J. (1987). Ankyrin binding to (Na + K )-ATPase and implications for the organization of membrane domains in polarized cells. Nature 328, 533-536. 

Hereditary spherocytosis Deficiencies in the amount or in the structure of a or p spectrin, ankyrin, band 3 or band 4.1... 

The major proteins (which include spectrin, ankyrin, the anion exchange protein, actin, and band 4.1) have been studied intensively, and the principal features of their disposition (eg, integral or peripheral), structure, and function have been established. 

Spectrin, Ankyrin, Other Peripheral Membrane Proteins Help Determine the Shape Flexibility of the Red Blood Cell... 

Ankyrin is a pyramid-shaped protein that binds spectrin. In mrn, ankyrin binds tightly to band 3, securing attachment of spectrin to the membrane. Ankyrin is sensitive to proteolysis, accounting for the appearance of bands 2.2, 2.3, and 2.6, all of which are derived from band 2.1. 

One cause of hereditary spherocytosis (Figure 52-5) is a deficiency in the amount of spectrin or abnormalities of its structure, so that it no longer tightly binds the other proteins with which it normally interacts. This weakens the membrane and leads to the spherocytic shape. Abnormalities of ankyrin and of bands 3 and 4.1 are involved in other cases. 

Axton JM, Shamanski FL, Young LM, Henderson DS, Boyd JB, Orr-Weaver TL 1994 The inhibitor of DNA replication encoded by the Drosophila gene plutonium is a small, ankyrin repeat protein. EMBO J 13 462-470... 

WJ Nelson, EM Shore, AZ Wang, RW Hammerton. (1990). Identification of a membrane-cytoskeletal complex containing the cell adhesion molecule uvomorulin (E-cadherin), ankyrin, and fodrin in Madin-Darby canine kidney epithehal cells. J Cell Biol 110 349-357. 

The specific domains that recognize KMe have been described within several protein families the so-called "royal family" of Tudor, Agenet, chromo, PWWP, and MBT domains the plant homeodomain (PHD) the WD40 repeat protein—WDR5 and ankyrin repeats [37,38]. Given the rapid rate of progress in this area, the relatively low affinity of these interactions (Kd values typically 10-100 jjM), the wide variety of... 

Mechanical functions of cells require interactions between integral membrane proteins and the cytoskeleton 29 The spectrin-ankyrin network comprises a general form of membrane-organizing cytoskeleton within which a variety of membrane-cytoskeletal specializations are interspersed 29 Interaction of rafts with cytoskeleton is suggested by the results of video microscopy 29... 

In erythrocytes and most other cells, the major structural link of plasma membranes to the cytoskeleton is mediated by interactions between ankyrin and various integral membrane proteins, including Cf/HCOj antiporters, sodium ion pumps and voltage-dependent sodium ion channels. Ankyrin also binds to the =100 nm, rod-shaped, antiparallel a(3 heterodimers of spectrin and thus secures the cytoskeleton to the plasma membrane. Spectrin dimers self-associate to form tetramers and further to form a polygonal network parallel to the plasma membrane (Fig. 2-9D). Neurons contain both spectrin I, also termed erythroid spectrin, and spectrin II, also termed fodrin. Spectrin II is found throughout neurons, including axons, and binds to microtubules, whereas spectrin I occurs only in the soma and dendrites. 

This spectrin network further binds to actin microfilaments and to numerous other ligands. These associations are probably dynamic. For example, phosphorylation of ankyrin can alter its affinity for spectrin. The functions of the multiple protein-interaction domains of both spectrin and ankyrin have been as yet only partially defined (see Ch. 8). 

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