A-spectrin

Myocardial infarcts Ca2+ homeostasis is lost in ischemic areas, triggering inappropriate calpain activity. Desmin and a-spectrin are degraded in ischemic hearts by synthetic calpain inhibitors. Protein and mRNA levels of m and (./-calpain increase after myocardial infarction40-43... 

Multiple sclerosis The 150-kDa calpain specific degradation product of a-spectrin increases 50% in human MS plaques.44 Degradation of the 68-kDa neurofilament protein is inhibited by a synthetic calpain inhibitor45... 

Fig. 6 A general pulse sequence (a) for spin diffusion or third-spin assisted mixing for polarization transfer between carbons (as shown) or carbon and nitrogen along with examples of homonuclear mixing elements and illustration of activated parts of H-13C-13C spin systems for PDSD, MIRROR, and PAR (b) (taken from [18] with permission), (c) Example of the application of PDSD for structure determination of the a-spectrin SH3 domain (taken from [133] with permission)...

Robust decreases in the expression of the various proteasome subunits and ubiquitin-conjugating enzymes have been described in prefrontal cortex in schizophrenia. Neuronal ubiquitin and proteasomes play an important role in the assembly, function and plasticity of the synapse. Structural proteins including tubulin and a-spectrin also show decreased expression in prefrontal cortex. 

A primary function of the SH3 domains is to form fimctional oligomeric complexes at defined subcellular sites, frequently in cooperation with other modular domains. SH3 domains are foimd in many proteins associated with the cytoskeleton or with the plasma membrane. Examples are the actin binding protein a-spectrin and myosin lb. Furthermore, SH3 interactions are involved in signal transduction in the Ras pathway (see Chapter 9). 

Circular dichroism (CD) Estimation of secondary structures a-Spectrin [48]... 

Fourier Deconvolution. Pairs of spin labels were introduced in the N-terminus of a-spectrin.66 Distances in the range of 8.3 to 11.7 A were determined by Fourier deconvolution of the dipolar broadening. The trends in distances for positions i to i+2, i + 3, i+4, and i + 5 were consistent with an a-helix. 

Figure 8.2. Schematic diagram of an erythrocyte membrane viewed from inside. The scale of the molecules has been expanded relative to the scale of the cell by about two orders of magnitude, a. Spectrin, b. Actin. c. Ankyrin. d. Anion transporter, e. Protein 4.1./. Glycophorin. g. Adducin. h. Lipid bilayer.

Sahr, K., Laurila, P., Kotula, L., Scarpa, E., Coupal, E., Leto, T., Linnenbach, A., Winkelmann, J., Speicher, D., Marchesi, V., Curtis, P., and Forget, B. (1990). The complete cDNA and polypeptide sequences of human erythroid a-spectrin. / Biol. Chem. 265, 4434-4443. 

N-terminal actin-binding domains and in the spectrin repeats that form the rod domains (Davison and Critchley, 1988). The spectrin repeats are found in distinct multiples in each protein, resulting in a characteristic actin crosslinking distance. a-Actinin contains four repeats, /3-spectrin contains 17, a-spectrin contains 20, and dystrophin contains 24. The sequences of some spectrin repeats of a- and /3-spectrin are similar in many ways to the four repeats present in a-actinin (Dubreuil, 1991). Within the cell, a-actinin and spectrin dimerize, although the spectrins interact further to generate a functional tetramer (Fig. 1). Most notable is that the ends of the native spectrin tetramer involved in the dimerization event show remarkable similarity to the rod domain repeats of a-actinin that also mediate dimer formation. 

Indeed, homologous regions of all of the a-actinin protein domains can be found within the sequences of a- and /3-spectrin. For example, the amino and carboxy terminal regions of a-actinin resemble the N-terminus of /3-spectrin and the C-terminus of a-spectrin, respectively (Byers et al, 1989 Dubreuil et al, 1989). Phylogenetic analysis shows a common ancestor for the first repeat of a-actinin and the first repeat of /3-spectrin. Similarly, each of the remaining repeats in a-actinin (2—4) correspond to repeats 1 and 2 of /3-spectrin and repeats 19 and 20 of a-spectrin respectively (Fig. 2). This may have relevance for the function of these repeats in the dimerization of these proteins (Pascual et al, 1997). It is the similarity between these regions of a-actinin, the spectrins, and the simpler domain organization of a-actinin that have led to the hypothesis that these two protein families have evolved from an a-actinin-like precursor. 

Each of the three EF-hand structures solved from the spectrin family proteins exhibit unique structural and functional differences, even though all are fundamentally similar. The a-spectrin (nonerythroid) EF hands bind calcium and presumably perform some kind of regulatory role regarding the actin-binding function of spectrin (Trave et al., 1995). Due to the low calcium affinity, it is expected that calcium regulatory events involving spectrin would occur in areas of the cell that would experience a transient but significant fluctuation of calcium concentration (Buevich et al., 2004). It is possible that the calcium-bound form of... 

The Src homology 3 (SH3) domain of a-spectrin was the first SH3 domain structure to be solved (Musacchio et al., 1992). The domain was initially identified as regions of similar sequence found within signaling proteins, such as the Src family of tyrosine kinases, the Crk adaptor... 

Spectrin forms an integral part of the erythrocyte cytoskeletal architecture any defects that disrupt the association of the spectrin heterotetra-mer or the interaction with any of the other submembranous proteins can result in RBC defects (reviewed in Hassoun and Palek, 1996). Indeed, abnormalities of the /3-spectrin N-terminus and the a-spectrin G-terminus affect the self-association site and result in hereditary elliptocytosis and hereditary pyropoikilocytosis (Delaunay, 1995 Delaunay and Dhermy, 1993 Palek and Jarolim, 1993). 

Becker, P. S., Tse, W. T., Lux, S. E., and Forget, B. G. (1993). Beta spectrin kissimmee A spectrin variant associated with autosomal dominant hereditary spherocytosis and defective binding to protein 4.1./. Clin. Invest. 92, 612-616. 

C. Hdtianu, L Bogdan, E Constantinescu, and M, Simionescu. Endothelial cells ex press a spectrin-like cyto skeletal protein. Circ. Res. 5ft605-7M (1986). 

C. Heltianit, I. Bogdan, E. Constandnescu, and M. Simionescu. Endothelial cells express a spectrin-like cytoakeletal protein. Clrc, Res. 58 605 (1986). 

The major components of the membrane skeleton are spectrin, actin, and protein 4.1. Spectrin is a highly flexible, rodlike molecule composed of two nonidentical polypeptides a-spectrin and (3-spectrin.These chains are aligned side by side in the form of a a(3-heterodimer, and spectrin heterodimers in turn join head to head to form (aP)2-tetramers. The tail ends of spec-... 

Because of the heterogeneous molecular nature of HS (Table 6-2), the HS genes can be assigned to several chromosomes chromosome 1 (a-spectrin), chromosome 8 (ankyrin), chromosome 14 ((3-spectrin), chromosome 15 (protein 4.2), and chromosome 17 (band 3). The... 

Connexins interact with other proteins within the cell. Recent studies suggest an association between Cx43 and the peripheral membrane protein ZO-1 in rat cardiomyocytes.13 ZO-1 - in turn - binds to a-spectrin, a protein which is highly expressed at... 

Upregulation of the lysosomal system has been suggested to contribute to the pathogenesis of AD. Okadaic acid (OA), a protein phosphatase-2A inhibitor, increases tau phosphorylation, p-amyloid deposition, and neuronal cell death. While inhibition of cathepsin D and L failed to protect neurons from OA-induced cell death, CA074-Me, a cathepsin B inhibitor, conferred a protective effect. CA-074Me reduced APP accumulation and a-spectrin cleavage, similar to the effect of calpain inhibition [507]. 

The backbone and side-chain and N signals of a solid 62-residue (U- C, N)-labelled protein containing the a-spectrin SH3 domain were assigned by 2D MAS N- C and dipolar correlation spectroscopy at... 

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