Joint-based description of protein structure: its application to the geometric characterization of membrane proteins

Abstract

A macroscopic description of a protein structure allows an understanding of the protein conformations in a more simplistic manner. Here, a new macroscopic approach that utilizes the joints of the protein secondary structures as a basic descriptor for the protein structure is proposed and applied to study the arrangement of secondary structures in helical membrane proteins. Two types of dihedral angle, Ω and λ, were defined based on the joint points of the transmembrane (TM) helices and loops, and employed to analyze 103 non-homologous membrane proteins with 3 to 14 TM helices. The Ω-λ plot, which is a distribution plot of the dihedral angles of the joint points, identified the allowed and disallowed regions of helical arrangement. Analyses of consecutive dihedral angle patterns indicated that there are preferred patterns in the helical alignment and extension of TM proteins, and helical extension pattern in TM proteins is varied as the size of TM proteins increases. Finally, we could identify some symmetric protein pairs in TM proteins under the joint-based coordinate and 3-dimensional coordinates. The joint-based approach is expected to help better understand and model the overall conformational features of complicated large-scale proteins, such as membrane proteins.

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

“…neighboring elements both at residues and secondary structures level have influence on each other and that can be identified by the distribution of their dihedral angles 44 – 46 . Our new joint-derived dihedral angles such as β and γ distributions were related to the structural arrangement of β-stands for both β-barrels TM and β-barrels cytoplasm architecture just as previously demonstrated with TM helical proteins using Ω and λ dihedral angles 37 . The dihedral angle between the joints is not only associated with the arrangements of the individual β-strands and loops but also involves in the dependency of adjacent secondary structural element orientations.…”

“…The overall distribution can possibly assist to understand the similarities and dissimilarities in their structural arrangement patterns. Overall β and γ distributions are restricted to certain regions for β-barrels TM indicating they show conformationally similar arrangements that are observed in Ω-λ plot for TM helical proteins 37 . On the other hand, β and γ distributions for β-barrels cytoplasm are sparsely distributed over greater regions signifying dissimilar patterns in their arrangements than the membrane counterparts.…”

“…The present study deals in relation to the recently developed joint-based description of protein structures. To understand the macroscopic geometric features of both TM and cytoplasmic β-barrel proteins such as their conformational distribution and the arrangements of β-strands, we utilize the joint constraint principles that were previously prepared to represent TM helices 37 . These β-barrel proteins always show consecutive elements of β-strands and loops linked one another as described in Fig.…”

“…Like TM helical proteins, a set of joints connecting the individual β-strands and loops were selected to describe a β-barrel geometry based on the joint-based description approach. Specifically, the Cα carbon coordinates of the first and last residues of each β-strand were considered as structural joining points as they represent the basic elements of protein structures 37 , 38 . The spatial arrangement of such joint points was measured by the dihedral angles between them.…”

“…In the present study, we attempted to perform a systematic comparison of β-barrels TM and β-barrels cytoplasm geometries using the joint-based description approach 37 , 38 . For comparison, structures of high-resolution, non-homologous β-barrels TM and β-barrels cytoplasm protein structures were obtained from the PDB and grouped based on their geometric analyses.…”