Sequence complexity of amyloidogenic regions in intrinsically disordered human proteins

Swagata Das; Uttam Pal; Supriya Das; Khyati Bagga; Anupam Roy; Arpita Mrigwani; Nakul C Maiti

doi:10.1371/journal.pone.0089781

Sequence complexity of amyloidogenic regions in intrinsically disordered human proteins

PLoS One. 2014 Mar 3;9(3):e89781. doi: 10.1371/journal.pone.0089781. eCollection 2014.

Authors

Swagata Das¹, Uttam Pal¹, Supriya Das¹, Khyati Bagga¹, Anupam Roy¹, Arpita Mrigwani¹, Nakul C Maiti¹

Affiliation

¹ Structural Biology and Bioinformatics Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology (IICB), Kolkata, India.

Abstract

An amyloidogenic region (AR) in a protein sequence plays a significant role in protein aggregation and amyloid formation. We have investigated the sequence complexity of AR that is present in intrinsically disordered human proteins. More than 80% human proteins in the disordered protein databases (DisProt+IDEAL) contained one or more ARs. With decrease of protein disorder, AR content in the protein sequence was decreased. A probability density distribution analysis and discrete analysis of AR sequences showed that ∼8% residue in a protein sequence was in AR and the region was in average 8 residues long. The residues in the AR were high in sequence complexity and it seldom overlapped with low complexity regions (LCR), which was largely abundant in disorder proteins. The sequences in the AR showed mixed conformational adaptability towards α-helix, β-sheet/strand and coil conformations.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Amyloid / chemistry*
Humans
Intrinsically Disordered Proteins / chemistry*
Molecular Sequence Data
Protein Structure, Secondary

Substances

Amyloid
Intrinsically Disordered Proteins

Grants and funding

This work was supported by grants GENESIS (BSC0121) and miND from the Council of Scientific & Industrial Research (CSIR), India. The funders have no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.