The β-link motif in protein architecture.

David P Leader,E James Milner-White

doi:10.1107/s2059798321006768

David P Leader, E James Milner-White

Open Access

https://doi.org/10.1107/s2059798321006768

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Abstract

The β-link is a composite protein motif consisting of a G1β β-bulge and a type II β-turn, and is generally found at the end of two adjacent strands of antiparallel β-sheet. The 1,2-positions of the β-bulge are also the 3,4-positions of the β-turn, with the result that the N-terminal portion of the polypeptide chain is orientated at right angles to the β-sheet. Here, it is reported that the β-link is frequently found in certain protein folds of the SCOPe structural classification at specific locations where it connects a β-sheet to another area of a protein. It is found at locations where it connects one β-sheet to another in the β-sandwich and related structures, and in small (four-, five- or six-stranded) β-barrels, where it connects two β-strands through the polypeptide chain that crosses an open end of the barrel. It is not found in larger (eight-stranded or more) β-barrels that are straightforward β-meanders. In some cases it initiates a connection between a single β-sheet and an α-helix. The β-link also provides a framework for catalysis in serine proteases, where the catalytic serine is part of a conserved β-link, and in cysteine proteases, including Mpro of human SARS-CoV-2, in which two residues of the active site are located in a conserved β-link.

Highlights

The two major architectural features of proteins – -helix and -sheet – occur where a suitable pair of dihedral angles is repeated along the backbone, leading to extensive hydrogen bonding
We have recently shown that two classes of G1 -bulge can be distinguished on the basis of the conformation of the residue preceding the doubleton: G1, where the conformation is R, and G1, where it is R (Leader & Milner-White, 2021)
The -links in the database were determined from SQL queries of the Protein Motif 2 database for structures with the three hydrogen bonds shown in the inset in Fig. 1, together with a requirement that the dihedral angles of residue 2 be within the R region of the Ramachandran plot

Summary

Introduction

The two major architectural features of proteins – -helix and -sheet – occur where a suitable pair of dihedral angles is repeated along the backbone, leading to extensive hydrogen bonding. Materials and methods differs from most other small hydrogen-bonded motifs, which This work employed a new MySQL relational database – result in either turns or indentations in proteins This Protein Motif 2 – containing structural information from a set composite motif has not received much attention since it was of 4484 individual protein subunits derived from the originally described (Richardson et al, 1978). The -links in the database were determined from SQL queries of the Protein Motif 2 database for structures with the three hydrogen bonds shown in the inset, together with a requirement that the dihedral angles of residue 2 be within the R region of the Ramachandran plot. Positions in these proteins corresponding to -links in the database were identified either by visual inspection using the 3D protein graphics program Jmol (Herraez, 2006) or, where necessary, with the multiple sequence alignment program ClustalX (Larkin et al, 2007)

Assignment of b-links to architectural components of proteins

Other b-links

Discussion