Polyalanine repeats

An elegant NMR experiment by the group of Lynn Jelinski at Cornell University has established that at least part of the microcrystals is built up from the polyalanine repeats in the protein chains. These experiments, which were made on C-enriched proteins produced by feeding the spiders C-labeled alanine, showed that there were two populations of alanine side chains, one ordered and oriented perpendicular to the fiber axis and a second less ordered. Jelinski s interpretation is that parts of the polyalanine sequences are incorporated as p strands in the microcrystals with an orientation parallel to the fiber axis. Whether or not the Gly-Gly-X repeats also form P strands in the microcrystals remains an open question. 

Polyalanine repeats. Our analysis of the constraints on repeat composition revealed that long stretches of alanine residues were almost as protective as the original GAr consensus. Interestingly, expansion of polyalanine stretches in core binding factor al (Mundlos et al., 1997), HoxDIS (Muragaki et al., 1996), polyalanine binding protein-2 (Brais et al.. 

Most silkworm cocoon and spider dragline silk fibers contain assembled antiparallel p-pleated-sheet crystalline structures [33-35]. Silks are considered semicrystalline materials with 30-50% crystallinity in spider silks, 62-65% in cocoon silk fibroin from the silkworm B. mori, and 50-63% in wild-type silkworm cocoons. In the -sheet erystals the polymer chain axis is parallel to the fiber axis. The extent to which these struetures form, as well as their orientation and size, directly impact the mechanical features of silk fibers. Furthermore, the polyalanine repeats or... 

Sfi.F-Test 19.4B Write the formula for (a) the monomer of poly(methyl methacrylate), used in contact lenses (17) (b) two repeating units of polyalanine, the polymer of the amino acid alanine, CH,CH(NH2)COOH. 

A spider s orb-web is formed by extrusion of a concentrated protein solution and stretching of the resulting fiber. The cross-strands, which are stronger than steel, resemble silkworm silk. The molecules contain microcrystalline p sheet domains that are rich in Gly-Ala repeats as well as polyalanine segments. The capture spiral is formed from much more elastic molecules that contain many -tum-forming sequences. These assume a springlike p spiral. See Box 2-B. 

Twelve or more additional triplet repeat diseases, many with neurological symptoms, have been identified (Table 26-4).405 407a These involve other trinucleotide repeats 5 -(GCG) , 5 -(CTG) , 5 -(GAA) , and 5 -(CAG) . In synpolydactyly, an inherited developmental defect causing malformation of hands and feet, an expansion of a GCG trinucleotide occurs within the gene HoxD 13. This results in incorporation of a polyalanine tract near the N terminus of the protein.408 Myotonic dystrophy DM1 (Box 19-A) results from expansion of CTG to 6 kbp or more within the untranslated 3 region of a gene for cAMP-dependent protein kinase.405 The mRNA transcripts accumulate... 

The primary structure of the silk fibroin from S.c. ricini has recently been determined by Yukihiro et al. (personal communication). The silk mainly consists of about 100 repeated similar sequences where there are alternative appearances of a polyalanine region and a glycine-rich region as in spider (major ampullate) silk. As a result, the most striking conformational characteristic of these silk fibroins in the silk gland or in aqueous solution is the presence of a-helical domains consisting of Ala residues. 

An isotactic chain is truly chiral if two bonds connecting a C atom with neighboring main-chain atoms are distinguishable or, more generally, if the directional chain stmcture follows from the stmcture of each repeat unit. Important chiral stmctures of that sort are provided by natural polyp>eptides (proteins) that are normally perfectly stereoregular (isotactic). For example, an isotactic polyalanine peptide chain, -CO-CHR-NH- (R=CH3, Figure 8), is chiral because reversing the... 

Solid-state NMR study of structural heterogeneity in peptides containing both polyalanine and repeated GGA sequences as a local structural model of Nephila clavipes dragline silk (Spidroin 1) has been reported. Solvent treatments prior to the NMR measurements were shown to induce a structural change in these model peptides. Conformation-dependent NMR chemical shifts were used to determine the local structure, including the evaluation of the fraction of several conformations. 

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