The Functional Significance of Hydrophobic Residue Distribution in Bacterial Beta-Barrel Transmembrane Proteins

Abstract

β-barrel membrane proteins have several important biological functions, including transporting water and solutes across the membrane. They are active in the highly hydrophobic environment of the lipid membrane, as opposed to soluble proteins, which function in a more polar, aqueous environment. Globular soluble proteins typically have a hydrophobic core and a polar surface that interacts favorably with water. In the fuzzy oil drop (FOD) model, this distribution is represented by the 3D Gauss function (3DG). In contrast, membrane proteins expose hydrophobic residues on the surface, and, in the case of ion channels, the polar residues face inwards towards a central pore. The distribution of hydrophobic residues in membrane proteins can be characterized by means of 1–3DG, a complementary 3D Gauss function. Such an analysis was carried out on the transmembrane proteins of bacteria, which, despite the considerable similarities of their super-secondary structure (β-barrel), have highly differentiated properties in terms of stabilization based on hydrophobic interactions. The biological activity and substrate specificity of these proteins are determined by the distribution of the polar and nonpolar amino acids. The present analysis allowed us to compare the ways in which the different proteins interact with antibiotics and helped us understand their relative importance in the development of the resistance mechanism. We showed that beta barrel membrane proteins with a hydrophobic core interact less strongly with the molecules they transport.

In Silico Modeling of the Influence of Environment on Amyloid Folding Using FOD-M Model

“…The modified FOD-M model was validated previously on the basis of membrane proteins [ 49 ]. The modification introduced in the FOD-M model with the parameter K, taking into account other environmental factors, allows the assessment of the status of amyloid proteins from the point of view of the participation of these external factors.…”

“…The simulation of the protein-folding process should be performed in an environment expressed by the distribution of 3DG and in an environment that gradually changes through an increase in the K value. As shown in [ 37 , 49 ], the K value turns out to be specific for a given protein. Further analysis of proteins for the corresponding K parameter value is performed on a large database.…”

“…On the basis of the analysis of such proteins (unfortunately, it is not a large group), one can speculate as to the structural changes of other amyloids with the only known structure of the amyloid form [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. The FOD-M modification presented in detail in [ 49 ] used to describe the spectrum of proteins differing in the degree of hydrophobicity order in relation to the assumed 3D Gaussian distribution justifies the use of this model for protein description. Since the introduced model, aimed at the interpretation of the specific structure of amyloids, requires interpretation in terms of a wider spectrum of protein structures, the analysis was extended to include the group of other amyloids [ 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]: prion proteins were included [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ], a group of proteins identified as intrinsically disordered due to their discussed predisposition to amyloid transformation [ 68 , 69 , 70 , 71 , 72 , 73 , 74 ], and short peptides both in their monomeric form and in the form of complexes [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ,…”

“…In order not to limit the proteins directly or indirectly related to the phenomenon of amyloidosis, the spectrum of the analyzed proteins was extended to include non-complexing proteins [88][89][90][91][92][93][94][95], a representative of enzymes [96,97], and a transmembrane protein [98]. The latter are discussed in detail in [37,49]. These lists do not exhaust the full range of the protein groups mentioned.…”

Dependence of Protein Structure on Environment: FOD Model Applied to Membrane Proteins

“…To assess the structures of the membrane proteins, a modified version of the FOD-M model was used, taking into account the presence of an environment not limited only to the aquatic environment [9]. The FOD model assumes that a polypeptide chain composed of bipolar molecules aims to create a micelle-like structure, concentrating hydrophobic residues in the center with simultaneous exposure of polar residues on the surface [10].…”