Protein Secondary Structure Patterns in Short-Range Cross-Link Atlas.

Area of Science:

• Structural Biology
• Computational Biology
• Biophysics

Background:

• Cross-linking mass spectrometry (XL-MS) is crucial for understanding protein structure and interactions.
• Short-range cross-links (<20 residues apart) are underutilized, limiting comprehensive structural analysis.

Purpose of the Study:

• To systematically analyze short-range cross-links and their relationship with protein secondary structure.
• To introduce X-SPAN software for integrating XL-MS data with protein structure predictions.
• To establish new methods for benchmarking protein structure prediction accuracy and XL-MS data quality.

Main Methods:

• System-wide analysis of publicly available XL-MS datasets.
• Integration of XL-MS data with AlphaFold-predicted protein structures using X-SPAN software.
• Statistical analysis of cross-linking patterns in relation to secondary structural elements (α-helices, coils, β-strands).

Main Results:

• Short-range cross-links exhibit distinct patterns correlated with protein secondary structures.
• α-helices show periodic cross-linking, while coils and β-strands display monotonic distributions.
• A protein grammar model enhances the specificity of short-range cross-links.

Conclusions:

• Short-range cross-links provide valuable information about local protein secondary structures.
• X-SPAN facilitates the exploration of secondary structure rearrangements and their functional implications.
• The study offers a framework for improving protein structure prediction and XL-MS data quality control.