The β-link motif in protein architecture

Area of Science:

• Protein structure and bioinformatics
• Structural biology
• Enzymology

Background:

• The β-link is a composite protein motif comprising a G1β β-bulge and a type II β-turn.
• It typically resides at the interface of two adjacent antiparallel β-sheet strands.
• This motif positions the N-terminal polypeptide segment perpendicularly to the β-sheet.

Purpose of the Study:

• To investigate the prevalence and location of the β-link in protein folds within the SCOPe classification.
• To identify specific protein structures and functional roles associated with the β-link motif.
• To explore the involvement of the β-link in protein catalysis.

Main Methods:

• Analysis of protein structures from the SCOPe (Structural Classification of Proteins) database.
• Identification and mapping of β-link motifs within different protein folds.
• Comparative analysis of β-link occurrences in various structural classes, including β-sandwiches, small β-barrels, and connections to α-helices.

Main Results:

• The β-link is frequently observed in specific locations within protein folds, connecting β-sheets to other protein regions.
• It is prevalent in β-sandwiches and small β-barrels (4-6 strands), linking β-strands across the barrel's open end.
• The β-link is absent in larger β-barrels (≥8 strands) and can link β-sheets to α-helices.
• Conserved β-links form the catalytic framework in serine proteases and cysteine proteases, including SARS-CoV-2 M^pro.

Conclusions:

• The β-link is a significant structural motif that plays a key role in the architecture of various protein folds.
• Its specific location and conserved nature highlight its importance in protein structure and function.
• The β-link serves as a critical framework for enzymatic catalysis in important protease families.