Glycine-alanine repeat

Sharipo A, Imreh M, Leonchiks A, Imreh S, and Masucci MG (1998) A minimal glycine-alanine repeat prevents the interaction of ubiquitinated iKB-a with the proteasome a new mechanism for selective inhibition of proteolysis. Nat. Med. 4 939-944. 

Standard peptide coupling chemistry is performed (Box 25). The acid component is transformed to an activated ester derivative and then treated with the amine [17-19]. This procedure is repeated twice. In the final step the ligands la-le-H4 are deprotected by aryl ether cleavage with BBr3. By use of this simple reaction sequence derivatives with glycine, alanine, phenylalanine, valine, leucine, and other amino acids as spacers were obtained [16]. 

Figure 2.12. Conformational plot for glycine-alanine. Plot of allowable angles for peptides containing a repeat unit of glycine and alanine showing totally (outer solid lines) and partially (inner solid lines) allowed conformations determined from normal and minimum interatomic distances.

Repeating sequences of amino acids with small, compact R-groups (e.g., glycine, alanine) tend to form the (3, or pleated sheet, structure, which consists of parallel (Fig. 2-3a) or antiparallel (Fig. 2-36) polypeptide chains linked by interchain hydrogen bonds. Silk is an example of the antiparallel sheet. 

The X-ray diffraction diagram gives a repeat period of 6-95 A (0-695 ftm), which is extremely close to two amino-acid residues fully extended which would be 3-5 A (0-35 nm) each. The structural unit which gives the pattern is probably the glycine alanine residue. 

A third polymorph, silk III, has also been described based on the interfacial behavior of the silkworm silk fibroin and the partitioning behavior at an air-water interface [44, 45]. Silk III, a structure stabilized at interfaces optimizes the surfactancy of the silk in the core repeats of glycine, alanine, and serine. 

Figure 1.3 Repeating chemical structure of silk fibroin, composed of the amino acid sequence glycine-serine-glycine-alanine-glycine-alanine. ...

Other fibrous proteins contain extensive regions of pleated sheets. The fibers spun by a silkworm, for example, are made almost entirely of fibroin, a protein composed primarily of just three amino acids glycine (45%), alanine (30%), and serine (12%). Each chain of fibroin contains extensive regions where a sequence of six amino acids occurs repeatedly . .. -Gly-Ser-Gly-Ala-Gly-Ala-. .. Notice that every other amino acid is glycine, which is the smallest amino acid. This alternating arrangement is an important feature in the packing of the strands that make up the pleated sheet. 

I-Solenoid repeats usually have several x or x x sequence patterns that correspond to the /1-strands (here, denotes an apolar residue, and x is mostly polar but can be any residue except pro line). The middle -position in x x usually has a bulky apolar residue, while -residues in positions close to turns are often alanine, glycine, serine, or threonine. These positions are also occupied by asparagine residues that stack to form H-bonded ladders inside the /1-solenoid. The strand-associated x and x x patterns are interrupted by regions enriched in polar residues and glycine (Hennetin et al., 2006). These are regions of turns and loops. The long loops frequently contain proline residues. In several /1-solenoids, the alternation of apolar and polar residues that is typical for /1-strands is not well observed and outside positions are occupied by apolar residues. 

A closer examination of the natural GAr sequence reveals that it is an imperfect repeat of single alanine amino acids separated by one to three glycine residues (Baer et al., 1984). Strikingly, the alanine residues are never adjacent to each other and never spaced by more than three glycine residues. To study the constraints of the repeat the iKB-a-GAr chimera were most helpful as short repeats of eight amino acids were sufficient for full... 

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