Intrinsically disordered proteins and structured proteins with intrinsically disordered regions have different functional roles in the cell

By Antonio Deiana, Sergio Forcelloni, Alessandro Porrello, Andrea Giansanti. 2019

117 citations recorded by the source corpus.

Many studies about classification and the functional annotation of intrinsically disordered proteins (IDPs) are based on either the occurrence of long disordered regions or the fraction of disordered residues in the sequence. Taking into account both criteria we separate the human proteome, taken as a case study, into three variants of proteins: i) ordered proteins (ORDPs), ii) structured proteins with intrinsically disordered regions (IDPRs), and iii) intrinsically disordered proteins (IDPs). The focus of this work is on the different functional roles of IDPs and IDPRs, which up until now have been generally considered as a whole. Previous studies assigned a large set of functional roles to the general category of IDPs. We show here that IDPs and IDPRs have non-overlapping functional spectra, play different roles in human diseases, and deserve to be treated as distinct categories of proteins. IDPs enrich only a few classes, functions, and processes: nucleic acid binding proteins, chromatin binding proteins, transcription factors, and developmental processes. In contrast, IDPRs are spread over several functional protein classes and GO annotations which they partly share with ORDPs. As regards to diseases, we observe that IDPs enrich only cancer-related proteins, at variance with previous results reporting that IDPs are widespread also in cardiovascular and neurodegenerative pathologies. Overall, the operational separation of IDPRs from IDPs is relevant towards correct estimates of the occurrence of intrinsically disordered proteins in genome-wide studies and in the understanding of the functional spectra associated to different flavors of protein disorder.

Subfields: Molecular Biology, Spectroscopy

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Robin Pearce
2. Yang Zhang
3. Debora Marks
4. Christopher Sander
5. Adam J. Riesselman
6. Jung-Eun Shin
7. A. Kruse
8. Conor McMahon

In Spectroscopy

1. Robin Pearce
2. Christopher Sander
3. Jian Tang
4. Debora Marks
5. Tom L. Blundell
6. Yang Zhang

Citations in the corpus

• Utilizing graph machine learning within drug discovery and development (2021, background): “However, ∼34% of proteins are classified as intrinsically disordered proteins with no 3D structure [211, 212].”
• Protein design and variant prediction using autoregressive generative models (2021, background): “…up 15 – 21% of human polymorphisms 41 – 43 , 44% of human proteins contain disordered regions longer than 30 amino acids 40,44 , and both are enriched in association with human diseases such as cystic fi brosis, many cancers 45,46 , cardiovascular and neurodegenerative diseases, and diabetes 47,48 .”
• Toward the solution of the protein structure prediction problem (2021, background): “An interesting exception to this are intrinsically disordered proteins, which have been estimated to make up roughly 30% of proteins in the human proteome, and may be functional despite lacking well-de fi ned tertiary structures (7).”