Why are ?natively unfolded? proteins unstructured under physiologic conditions?

2000/01/01 by Vladimir N. Uversky, Joel R. Gillespie, J. R. Gillespie +1 · 13 citations
Biochemistry, Genetics and Molecular Biology · Materials Science · #Enzyme Structure and Function #Hemoglobin structure and function #Protein Structure and Dynamics

paper · doi:10.1002/1097-0134(20001115)41:3<415::aid-prot130>3.0.co;2-7

openalex publication_date 2000/01/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

"Natively unfolded" proteins occupy a unique niche within the protein kingdom in that they lack ordered structure under conditions of neutral pH in vitro. Analysis of amino acid sequences, based on the normalized net charge and mean hydrophobicity, has been applied to two sets of proteins: small globular folded proteins and "natively unfolded" ones. The results show that "natively unfolded" proteins are specifically localized within a unique region of charge-hydrophobicity phase space and indicate that a combination of low overall hydrophobicity and large net charge represent a unique structural feature of "natively unfolded" proteins.

Citations

• A simple method for displaying the hydropathic character of a protein

Cited by

• Intrinsically disordered proteins in overcrowded milieu: Membrane-less organelles, phase separation, and intrinsic disorder
• FINCHES: A Computational Framework for Predicting Intermolecular Interactions in Intrinsically Disordered Proteins
• FlgM gains structure in living cells
• Conformations of intrinsically disordered proteins are influenced by linear sequence distributions of oppositely charged residues
• Design of intrinsically disordered protein variants with diverse structural properties
• Electrostatic Collapse of Intrinsically Disordered Acid-Rich Protein Is Sensitive to Counterion Valency
• Electrostatic Collapse of Intrinsically Disordered Acid-Rich Protein Is Sensitive to Counterion Valency
• Combining predictors of natively unfolded proteins to detect a twilight zone between order and disorder in generic datasets
• Sequence Analysis and Modeling of the Repetitive Region of the Long Isoform of Clarinet/CLA-1
• Oligomerization of 33‐mer Gliadin Peptides: Supramolecular Assemblies in Celiac Disease
• The Blobulator: A Toolkit for Identification and Visual Exploration of Hydrophobic Modularity in Protein Sequences
• Physicochemical Features and Peculiarities of Interaction of Antimicrobial Peptides with the Membrane
• 15N-detected TROSY for 1H-15N heteronuclear correlation to study intrinsically disordered proteins: strategies to increase spectral quality

Related

• Combining predictors of natively unfolded proteins to detect a twilight zone between order and disorder in generic datasets
• Number of natively unfolded proteins scales with genome size
• Protein Collapse is Encoded in the Folded State Architecture
• A Mean-Field Description of Protein Folding: Evolutional Conservation of Hydrophobicity Profile and Folding Nuclei
• Rethinking the protein folding problem from a new perspective