FuzDB: database of fuzzy complexes, a tool to develop stochastic structure-function relationships for protein...

Area of Science:

• Biochemistry
• Structural Biology
• Bioinformatics

Background:

• Proteins can maintain intrinsic disorder (ID) even when bound to partners.
• These intrinsically disordered regions play crucial roles in biological functions and complex assembly.
• Existing databases often lack a focus on the biological context and functional impact of ID regions in complexes.

Purpose of the Study:

• To compile and present experimentally observed fuzzy protein complexes.
• To focus on intrinsically disordered (ID) regions within a biological context, including higher-order assemblies.
• To provide a detailed analysis of structural and functional data for fuzzy protein regions.

Main Methods:

• Compilation of entries with structural evidence of dynamic disorder in partner-bound forms.
• Inclusion of in vitro or in vivo biological evidence for the significance of fuzzy regions.
• Classification of fuzzy regions based on topology and mechanism.

Main Results:

• FuzDB provides a curated collection of fuzzy protein complexes.
• Detailed analysis elucidates molecular mechanisms of fuzzy regions in protein assemblies.
• Identified regulatory sites from alternative splicing (AS) and post-translational modifications (PTMs).

Conclusions:

• FuzDB offers a unique resource for studying intrinsically disordered regions in protein complexes.
• The database facilitates understanding of how fuzzy regions impact protein assembly and function.
• FuzDB can aid in developing stochastic structure-function relationships and a new paradigm in protein science.