Structures of single‐layer β‐sheet proteins evolved from β‐hairpin repeats

Abstract

Free‐standing single‐layer β‐sheets are extremely rare in naturally occurring proteins, even though β‐sheet motifs are ubiquitous. Here we report the crystal structures of three homologous, single‐layer, anti‐parallel β‐sheet proteins, comprised of three or four twisted β‐hairpin repeats. The structures reveal that, in addition to the hydrogen bond network characteristic of β‐sheets, additional hydrophobic interactions mediated by small clusters of residues adjacent to the turns likely play a significant role in the structural stability and compensate for the lack of a compact hydrophobic core. These structures enabled identification of a family of secreted proteins that are broadly distributed in bacteria from the human gut microbiome and are putatively involved in the metabolism of complex carbohydrates. A conserved surface patch, rich in solvent‐exposed tyrosine residues, was identified on the concave surface of the β‐sheet. These new modular single‐layer β‐sheet proteins may serve as a new model system for studying folding and design of β‐rich proteins.

What is hidden in the darkness? Characterization of AlphaFold structural space

“…In Figure 3b, we show a cluster containing Outer Membrane β -Barrels but also other structurally similar proteins. In the middle of this cluster, there are a number of structural outliers (bigger circles) that consist of single layer beta-sheets, which are rare amongst natural proteins (Xu et al ., 2019). Many of these are Gloverins, antimicrobials targetting Gram-negative bacteria for which no homologs exist in the PDB (Yi et al ., 2014).…”

The Inhibition of Gag-Pol Expression by the Restriction Factor Shiftless Is Dispensable for the Restriction of HIV-1 Infection

“…Nevertheless, mutant ZRM CAAC2 but not mutant ZRM CAAC1 was capable of homotypic interactions and ribosome binding, suggesting that W119 and W120 may play an important role. One likely explanation could be that these aromatic residues are required to stabilize the folded domain [ 38 ] and that changes in folding, rather than alterations in specific side-chain interactions, are responsible for the lack of homotypic interactions of mutant ZRM CAAC1 .…”

A sequential-structural hybrid method for linear B-cell epitope prediction

“…Aromaticity according to [18] is simply the frequency of aromatic amino acids (Phenylalanine (Phe), Tyrosine (Tyr), Tryptophan(Trp)) in the hypothetical translated gene product. Aromatic residues are often found in important parts of the protein-protein or protein-ligand interaction interface across the protein, largely enclosed within the core of spherical proteins [19]. The author employs both aromaticity of peptide and protein in the structure-based features.…”