Expanding the proteome: disordered and alternatively folded proteins

Area of Science:

• Biochemistry
• Molecular Biology
• Genomics

Background:

• Proteins are traditionally viewed as functional only when well-structured and correctly folded.
• The human genome appears to code for fewer proteins than necessary, with many predicted to lack stable 3D structures.
• Experimental evidence reveals functional proteins that are partially or fully disordered in solution.

Purpose of the Study:

• To review recent advancements in the study of intrinsically disordered proteins (IDPs).
• To explore the biological rationales behind the widespread occurrence of protein disorder.
• To evaluate the roles of IDPs and partially structured proteins in biological systems.

Main Methods:

• Genome annotation studies to identify potential disordered protein sequences.
• Experimental characterization of protein structure and function in solution.
• Literature review of recent research on intrinsically disordered proteins.

Main Results:

• A significant proportion of protein sequences encoded by genomes are predicted to be intrinsically disordered.
• Intrinsically disordered proteins and domains exhibit diverse biological functions.
• The disorder-to-order continuum encompasses a range of protein structural dynamics.

Conclusions:

• Protein function is not solely dependent on stable three-dimensional structures.
• Intrinsically disordered proteins represent a significant and functionally important class of biomolecules.
• Understanding protein disorder is crucial for comprehending the full scope of proteome diversity and function.