The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease

In the 1960s, Christian Anfinsen postulated that the unique three-dimensional structure of a protein is determined by its amino acid sequence. This work laid the foundation for the sequence-structure-function paradigm, which states that the sequence of a protein determines its structure, and structu...

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Bibliographic Details
Published in:Biochemical Society transactions Vol. 44; no. 5; pp. 1185 - 1200
Main Author: Babu, M Madan
Format: Journal Article
Language:English
Published: England 15.10.2016
Subjects:
Alternative Splicing
Amino Acid Sequence
Apoptosis - genetics
Disease - genetics
Humans
Intrinsically Disordered Proteins - chemistry
Intrinsically Disordered Proteins - genetics
Intrinsically Disordered Proteins - metabolism
Models, Molecular
Protein Conformation
Protein Folding
Structure-Activity Relationship
protein turnover
RNA localization
alternative splicing
gene expression and regulation
intrinsically disordered proteins
biological networks
ISSN:1470-8752
Online Access:Get more information
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Summary:In the 1960s, Christian Anfinsen postulated that the unique three-dimensional structure of a protein is determined by its amino acid sequence. This work laid the foundation for the sequence-structure-function paradigm, which states that the sequence of a protein determines its structure, and structure determines function. However, a class of polypeptide segments called intrinsically disordered regions does not conform to this postulate. In this review, I will first describe established and emerging ideas about how disordered regions contribute to protein function. I will then discuss molecular principles by which regulatory mechanisms, such as alternative splicing and asymmetric localization of transcripts that encode disordered regions, can increase the functional versatility of proteins. Finally, I will discuss how disordered regions contribute to human disease and the emergence of cellular complexity during organismal evolution.
Bibliography:ObjectType-Article-2
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ObjectType-Review-1
ISSN:1470-8752
DOI:10.1042/bst20160172