Geometrical and Sequence Characteristics of α-Helices in Globular Proteins

Abstract

Understanding the sequence-structure relationships in globular proteins is important for reliable protein structure prediction and de novo design. Using a database of 1131 alpha-helices with nonidentical sequences from 205 nonhomologous globular protein chains, we have analyzed structural and sequence characteristics of alpha-helices. We find that geometries of more than 99% of all the alpha-helices can be simply characterised as being linear, curved, or kinked. Only a small number of alpha-helices ( approximately 4%) show sharp localized bends in their middle regions, and thus are classified as kinked. Approximately three-fourths (approximately 73%) of the alpha-helices in globular proteins show varying degrees of smooth curvature, with a mean radius of curvature of 65 +/- 33 A; longer helices are less curved. Computation of helix accessibility to the solvent indicates that nearly two-thirds of the helices ( approximately 66%) are largely buried in the protein core, and the length and geometry of the helices are not correlated with their location in the protein globule. However, the amino acid compositions and propensities of individual amino acids to occur in alpha-helices vary with their location in the protein globule, their geometries, and their lengths. In particular, Gln, Glu, Lys, and Arg are found more often in helices near the surface of globular proteins. Interestingly, kinks often seem to occur in regions where amino acids with low helix propensities (e.g., beta-branched and aromatic residues) cluster together, in addition to those associated with the occurrence of proline residues. Hence the propensities of individual amino acids to occur in a given secondary structure depend not only on conformation but also on its length, geometry, and location in the protein globule.

Structure and Dynamics of Micelle-bound Human α-Synuclein

“…1), indicating that dynamics is not significantly impacting the fragment structures over this length range. Standard deviations for the angles were typically between 2 and 10°for most residues, and between 10 and 25°for Ala 30 -Thr 44 . The local geometry thus defined was implemented as backbone dihedral restraints in subsequent structure calculations with the program Xplor-NIH 2.9.5 (38).…”

“…indicators of helix curvature (44,45). For helix-N the average circle diameter and bending angle were 153 Å and 10.1 Ϯ 5.2°, respectively, whereas for helix-C values of 82 Å and 10.7 Ϯ 6.8°, respectively, were obtained.…”

“…An average of 3.60 Ϯ 0.13 residues make up one turn of helix-N with an average twist angle of 100.1 Ϯ 3.8°; for helix-C these parameters are 3.56 Ϯ 0.16 and 101.2 Ϯ 4.7°. Those parameters are not very sensitive to deviations from linear ␣-helical geometry (44). The diameter of a circle best-fitted to the helix and the bending angle between successive local helix axes calculated for 4 residue stretches are better …”

“…Consequently, the structural implications arising from the less curved and larger surface available to aS in the vesicle-bound state have to be evaluated. An altered helix curvature in the vesicle, compared with the micelle-bound state, will have little effect on the number of residues per turn and helix twist (44). In other words, the local structure encoded by the aS amino acid sequence, which places side chains involved in favorable interactions with the vesicle surface on one side of the helix, remains the same.…”

“…In the presence of SUV the large majority of aS molecules exist vesicle-bound (10). Based on the backbone 1 H-1 H NOE and secondary chemical shift pattern, helical secondary structure has been attributed to the entire repeat region in the micelle-bound state with the exception of a short stretch near Ser 42 -Thr 44 (12,18). When associated with SUVs of 300 -400 Å diameter, electron paramagnetic resonance (EPR) data were interpreted as evidence for an uninterrupted helix extending throughout the entire repeat region (19).…”