Structural disorder: a tool for housekeeping proteins performing tissue-specific interactions

Area of Science:

• Molecular Biology
• Biophysics
• Structural Biology

Background:

• Tissue-specific interactions (TSIs) involve proteins unique to particular tissues.
• Housekeeping (HK) proteins, typically ubiquitous, are increasingly observed to participate in TSIs, a phenomenon requiring explanation.
• The mechanism by which single HK proteins mediate multiple TSIs remains an open question.

Purpose of the Study:

• To investigate the hypothesis that HK proteins possess structural flexibility enabling efficient modulation of TSIs.
• To explore the role of intrinsic disorder and domain structure in HK protein interactions.
• To understand the molecular basis for HK proteins mediating numerous TSIs.

Main Methods:

• Comparative analysis of protein structures and interaction interfaces.
• Assessment of intrinsic disorder propensity in HK versus tissue-specific proteins.
• Examination of domain composition and interface overlap with disordered regions.

Main Results:

• HK proteins exhibit a higher degree of intrinsic disorder compared to tissue-specific proteins.
• A larger proportion of interacting interfaces in HK proteins overlap with disordered segments.
• HK proteins involved in numerous TSIs preferentially adopt single-domain structures.

Conclusions:

• HK proteins adapt significant structural flexibility, particularly intrinsic disorder, to mediate TSIs effectively.
• The combination of structural flexibility and single-domain architecture offers an economic advantage for HK proteins.
• This adaptability allows HK proteins to achieve various conformations, optimizing molecular systems for diverse interactions.