Biology subjects

Deiana, A.

Publications and source records attributed to Deiana, A..

3 recordsLinked to original sources

bioRxiv2019

Variants of intrinsic disorder: structural characterization

In a recent study, we have introduced an operational classification of the human proteome in three variants of disorder: ordered proteins (ORDPs), structured proteins with intrinsically disordered protein regions (IDPRs), intrinsically disordered proteins (IDPs). That classification was useful in functionally separating IDPRs from IDPs, which up until now have been generally considered as a whole. In this study, we corroborate this distinction by considering different physical-chemical and structural properties. Both ORDPs and IDPRs are enriched in order-promoting amino acids, whereas only IDPs show an enrichment in disordered-promoting amino acids. Consistently, ORDPs and IDPRs are preferentially located in the ordered phase of the charge-hydropathy plot, whereas IDPs are widespread over the disordered phase. We introduce the mean packing - mean pairwise energy (MP-MPE) plane to structurally characterize these variants even in the absence of a structural model. As expected for well-packed proteins, a negative linear correlation is observed between MP and MPE for ORDPs and IDPRs, whereas IDPs break this linear dependence. Finally, we find that IDPs have a more extended conformation as measured by the scaling law between the radius of gyration and the length of these proteins, and accordingly they have higher solubility and accessible surface area than ORDPs and IDPRs. Overall, our results confirm the relevance of our operational separation of IDPRs from IDPs and provide further validation of our criteria to separate IDPs from the rest of human proteome.

bioinformatics↗

bioRxiv2019

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

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.

bioinformatics↗

bioRxiv2018

New Classification of Intrinsic Disorder in the Human Proteome

We propose a new, sequence-only, classification of intrinsically disordered human proteins which is based on two parameters: dr, the percentage of disordered residues, and Ld, the length of the longest disordered segment in the sequence. Depending on dr and Ld, we distinguish five variants: i) ordered proteins (ORDs); ii) not disordered proteins (NDPsj; (iii) proteins with intrinsically disordered regions (PDRs); iv) intrinsically disordered proteins (IDPs) and v) proteins with fragmented disorder (FRAGs). PDRs have been considered in the general category of intrinsically disordered proteins for a long time. We show that PDRs are closer to globular, ordered proteins (ORDs and NDPs) than to disordered ones (IDPs), both in amino acid composition and functionally. Moreover, NDPs and PDRs are uniformly spread over several functional protein classes, whereas IDPs are concentrated only on two, namely nucleic acid binding proteins and transcription factors, which are just a subset of the functions that are commonly associated with protein intrinsic disorder. As a conclusion, PDRs and IDPs should be considered, in future classifications, as distinct variants of disordered proteins, with different physical-chemical properties and functional spectra.

bioinformatics↗