Helix kinks are equally prevalent in soluble and membrane proteins

Abstract

Helix kinks are a common feature of α-helical membrane proteins, but are thought to be rare in soluble proteins. In this study we find that kinks are a feature of long α-helices in both soluble and membrane proteins, rather than just transmembrane α-helices. The apparent rarity of kinks in soluble proteins is due to the relative infrequency of long helices (≥20 residues) in these proteins. We compare length-matched sets of soluble and membrane helices, and find that the frequency of kinks, the role of Proline, the patterns of other amino acid around kinks (allowing for the expected differences in amino acid distributions between the two types of protein), and the effects of hydrogen bonds are the same for the two types of helices. In both types of protein, helices that contain Proline in the second and subsequent turns are very frequently kinked. However, there are a sizeable proportion of kinked helices that do not contain a Proline in either their sequence or sequence homolog. Moreover, we observe that in soluble proteins, kinked helices have a structural preference in that they typically point into the solvent.

Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin

“…Usually, the proline disrupts the ␣-helical structure by putting a kink in the polypeptide chain; in short amphipathic model peptides, the introduction of a proline in the middle of the nonpolar face determines a loss of approximately 50% of the helical content (50). The substitution of the proline with alanine induces a decrease in activity while maintaining the percentage of helical structures in TFE.…”

Benzene Probes in Molecular Dynamics Simulations Reveal Novel Binding Sites for Ligand Design

“…A recent survey of the Protein Data Bank (PDB) 43 reveals that this phenomenon is commonly found in long α-helices, occurring in 30% of membrane protein helices and 20% of length-matched (≥20 residues) globular protein helices. 44 Tyr100 and Tyr104, which line the proximal P27 site, are both rotated toward the peptide, relative to the WT p53-MDM2 complex structure (Figure 3B). Tyr100 forms an edge-to-face interaction with Phe/Tyr30 and a hydrogen bond with the backbone carbonyl of Leu26 from the peptides, while rotation of Tyr104 allows it to form a hydrogen bond with the hydroxyl of Tyr30 and slightly occlude the putative second nutlin binding site.…”

Directed Evolution of a Bright Near-Infrared Fluorescent Rhodopsin Using a Synthetic Chromophore

“…In E. coli , the apparent K d for merocyanine retinal decreased 2.5-fold from wild-type Arch to Mero-4 (from 3.25 to 1.33 μM), with the most significant decrease (1.8-fold) observed between WT and Mero-2 (Figure 5 B ). Combined, the two mutations of Mero-2 (P60S and G61L) likely affect the conformation of Helix 2 (Vonheijne, 1991; Wilman et al, 2014), possibly modifying the protein-Schiff base interaction. Of the two additional mutations in Mero-4, P196G may affect the conformation of Helix 4, and both P196G and S151A could expand the retinal-binding pocket to better accommodate the indolylidene ring of merocyanine retinal.…”