A crystal structure with features of an antiparallel α‐pleated sheet

Abstract

A single-crystal x-ray diffraction analysis of Boc-L-Ala-D-aIle-L-Ile-OMe has been carried out. The analysis has shown (a) that the tripeptide molecules have in part an alpha-extended conformation, the torsion angles of the L-Ala and D-aIle residues being psi 1 = -75.1 degrees and psi 1 = -25.8 degrees and psi 2 = 67.3 degrees and psi 2 = 44.1 degrees, respectively, and (b) that the molecules are organized in rippled planes where they occur in relative antiparallel orientation linked together side by side by H bonds. This molecular organization of the tripeptide corresponds closely to that of an antiparallel alpha-pleated sheet, and likely constitutes the first example of a structure of this kind for which a characterization at the atomic level has been achieved. A molecular dynamics study has shown that the molecular conformation of the tripeptide in the crystalline state is determined primarily by intermolecular interactions.

Quantum mechanical studies on model α‐pleated sheets

“…For example, the α L of Asn 608 in the NMR structure of janus-faced C2B domain of rabphilin (PDB entry: 3RPH) is (59.9°, 45.4°); the α L of Asn 207 in the crystal structure of C2 domain of snaptotagmin I (PDB entry: 1RSY) is (45.5°, 56.1°); and the α L of Asn 72 in the crystal structure of calcium phospholipid binding domain of cytosolic phospholipase A2 (PDB entry: 1RLW) is (53.2°, 52.4°). Our optimized α L dihedral angles are also close to those observed in the crystal structure of a capped tripeptide with features of α-pleated sheet, in which the dihedral angles of α L are (φ = 67.3±5°, ψ = 44.1±5°) 35. The α R dihedral angles of this tripeptide is (φ = -75.1±5°, ψ = -25.8±6°) 35.…”

Self-Assembling Organic Nanotubes

“…[41] In 1975 DeSantis and co-workers reported the first attempts at preparing b-helix-forming oligopeptides of discrete length. [39] In the solid state, peptides of general sequence X(l-Ala-d-Val) m Y displayed X-ray powder diffraction patterns consistent with a-pleated structures [28,29,42] while circular dichroism (CD) spectra of the polymer in trifluoroethanol (TFE) suggested a b-helical conformation. In addition, 1 H NMR spectra ([D 6 ]DMSO) of hexa-and octapeptides (X benzyloxycarbonyl (Cbz), Y OMe) were well dispersed and showed 3 J NH,aH values of nearly 8.5 Hz, which strongly evince b-type f torsion angles.…”

“…[57] The reduced steric bulk presumably results in a lesser degree of b-helical preorganziation in the backbone, allowing precipitation through the formation of a-pleatedsheet aggregates. [28,29,42] Introduction of a single backbone Nmethyl substituent at the (n À 3)-position abolished higher order aggregation and led to a mixture of soluble singlestranded b 4.4 -and double-stranded 45 b 5.6 -helices. [57] The foregoing studies underscore the strong influence of solvent, peptide length, amino acid composition, and terminating groups on b-helical structures, all of which complicate prediction of the pore size.…”

Designed α-sheet peptides inhibit amyloid formation by targeting toxic oligomers

“…Once a sheet is formed, a simple peptide plane flip could convert the α-sheet into a β-sheet and ultimately a mature fibril (Daggett, 2006). α-sheet structure has been observed in a peptide crystal structure (Di Blasio et al, 1994), and short stretches of α-strand are present in various proteins in the Protein Data Bank (Daggett, 2006), although extensive α-sheet formation has not been observed in native proteins.

10.7554/eLife.01681.003Figure 1.α-sheet conversion, conformational properties and peptide designs.( A ) β- to α-sheet conversion of transthyretin (as reported by Armen et al, 2004a, 2004b). The protein backbone is shown in cartoon representation with the region of interest (residues 105–121) shown as sticks.

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