Comparative Analysis of TM and Cytoplasmic β-barrel Conformations Using Joint Descriptor

Abstract

Macroscopic descriptors have become valuable as coarse-grained features of complex proteins and are complementary to microscopic descriptors. Proteins macroscopic geometric features provide effective clues in the quantification of distant similarity and close dissimilarity searches for structural comparisons. In this study, we performed a systematic comparison of β-barrels, one of the important classes of protein folds in various transmembrane (TM) proteins against cytoplasmic barrels to estimate the conformational features using a joint-based descriptor. The approach uses joint coordinates and dihedral angles (β and γ) based on the β-strand joints and loops to determine the arrangements and propensities at the local and global levels. We then confirmed that there is a clear preference in the overall β and γ distribution, arrangements of β-strands and loops, signature patterns, and the number of strand effects between TM and cytoplasmic β-barrel geometries. As a robust and simple approach, we determine that the joint-based descriptor could provide a reliable static structural comparison aimed at macroscopic level between complex protein conformations.

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

“…Although the association of amyloid-forming properties with protein domains is poorly studied, there is growing evidence that different functional and pathogenic amyloid-forming proteins of prokaryotes and eukaryotes contain β-barrel domains or form β-barrels under particular conditions in vitro or in vivo. Similarly to amyloids, β-barrels represent a highly specific type of β-strand-enriched fold [ 17 , 24 , 25 , 26 ], which is widespread in nature and is presented by both membrane and cytoplasmic proteins [ 27 ]. Comparably to amyloidogenic proteins, β-barrel proteins are rich in hydrophobic residues [ 28 ].…”

“…β-strands have a predominantly antiparallel orientation and are hydrogen-bonded to one another, which leads to the formation of β-sheets. When the first and last β-strands interact with a hydrogen bond, β-sheets are twisted into a cylindrical structure, resembling a barrel, from which the name of this type of fold is derived [ 25 , 27 , 29 , 30 ]. The similar topology of β-barrel proteins may indicate their common evolutionary origin.…”

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

“…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. The former study used 77 membrane barrels and 72 soluble barrels at ≤60% sequence identity, and the latter study used 29 membrane barrels and 51 soluble barrels at ≤30% sequence identity.…”

“…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 . Also the geometry of the β-barrel differs, especially with respect to their dihedral angles between membrane and soluble β-barrels . These studies used smaller data sets that also included nonclosed soluble barrels.…”

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

“…13 Also the geometry of the β-barrel 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.…”