β‐Strand twisting/bending in soluble and transmembrane β‐barrel structures

Abstract

The majority of β-strands in globular proteins have a right-handed twist and bend. The dominant driving force for β-strand twisting is thought to be inter-strand hydrogen bonds. We previously demonstrated that for water-soluble proteins, both the twisting and bending of β-strand are suppressed by the polar side chains of serine, threonine, and asparagine residues. To determine whether this also holds for transmembrane β-strands, we calculated and statistically analyzed the twist and bend angles of four-residue frames of β-strands in both transmembrane and water-soluble β-barrel proteins with known three-dimensional structures. In the case of transmembrane β-strands, we found that twisting was suppressed even for frames not containing serine, threonine, or asparagine residues. The suppression of twisting in transmembrane β-strands could be attributed to the propagation of the suppressive effect of serine, threonine, and asparagine residues within a frame to the neighboring, hydrogen-bonded strands under the restriction that all strands in the closed barrel structure must have similar twist angles. A similar tendency was also observed for water-soluble β-barrel proteins. We previously showed that the dominant driving force for β-strand bending is hydrophobic interactions involving aromatic residues within and outside the strand. Transmembrane β-barrels have no hydrophobic core; however, rather hydrophilic residues predominate inside the barrel or the β-strands of transmembrane β-barrels have larger bend angles than those of water-soluble β-barrels. Our results reveal that, in transmembrane β-barrel proteins, the glycine-aromatic ring motif is important for generating the β-strand bending necessary for barrel formation.

β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis

“…Despite the variety of structures and functions of β-barrel proteins, they can be divided into two major groups: (1) water-soluble proteins of prokaryotes and eukaryotes, and (2) membrane proteins that are found in the outer membranes of Gram-negative bacteria, mitochondria, and chloroplasts [ 33 , 34 ], and produced by several species of Gram-positive bacteria [ 35 ]. The main structural difference between water-soluble and membrane β-barrels is the orientation of their nonpolar and polar amino acid residues.…”

Membrane Barrels Are Taller, Fatter, Inside-Out Soluble Barrels

“…17 The structures of membrane and soluble β-barrels have been compared before, revealing that the eight stranded membrane barrels have a higher glycine content, are less twisted and more bent, and have smaller pores than their eight stranded soluble β-barrels counterparts. 18 Also the geometry of the β-barrel differs, especially with respect to their dihedral angles between membrane and soluble β-barrels. 19 These studies used smaller data sets that also included nonclosed soluble barrels.…”

Membrane barrels are taller, fatter, inside-out soluble barrels

“…37 Though it remains unclear what its role is in membrane β-barrels, some have suggested it is required for the larger bend angles inherent in membrane β-barrels. 13 We anticipate that the flexibility imparted by glycine and to a lesser extent alanine may also facilitate the complex process of membrane β-barrel insertion and folding into the membrane.…”

“…12 The structure of membrane and soluble β-barrels have been compared before, revealing that the eight stranded membrane barrels have a higher glycine content and are less twisted, more bent, and have smaller pores than their eight stranded soluble β-barrels counterparts. 13 Also the geometry of the βbarrel differs, especially with respect to their dihedral angles between membrane and soluble β-barrel. 14 These studies used smaller datasets that also included non-closed soluble barrels.…”