Comparative functional analysis of proteins containing low-complexity predicted amyloid regions

Kumari, Bandana and Kumar, Ravindra and Chauhan, Vipin and Kumar, Manish (2018) Comparative functional analysis of proteins containing low-complexity predicted amyloid regions. In: PEERJ, 6 .

PDF Pee_6_e5823_2018.pdf - Published Version Restricted to Registered users only Download (4MB) | Request a copy

Abstract

Background: In both prokaryotic and eukaryotic proteins, repeated occurrence of a single or a group of few amino acids are found. These regions are termed as low complexity regions (LCRs). It has been observed that amino acid bias in LCR is directly linked to their uncontrolled expansion and amyloid formation. But a comparative analysis of the behavior of LCR based on their constituent amino acids and their association with amyloidogenic propensity is not available. Methods: Firstly we grouped all LCRs on the basis of their composition: homo-polymers, positively charged amino acids, negatively charged amino acids, polar amino acids and hydrophobic amino acids. We analyzed the compositional pattern of LCRs in each group and their propensity to form amyloids. The functional characteristics of proteins containing different groups of LCRs were explored using DAVID. In addition, we also analyzed the classes, pathways and functions of human proteins that form amyloids in LCRs. Results: Among homopolymeric LCRs, the most common was Gln repeats. LCRs composed of repeats of Met and aromatic amino acids were amongst the least occurring. The results revealed that LCRs composed of negatively charged and polar amino acids were more common in comparison to LCRs formed by positively charged and hydrophobic amino acids. We also noted that generally proteins with LCRs were involved in transcription but those with Gly repeats were associated to translational activities. Our analysis suggests that proteins in which LCR is composed of hydrophobic residues are more prone toward amyloid formation. We also found that the human proteins with amyloid forming LCRs were generally involved in binding and catalytic activity. Discussion: The presented analysis summarizes the most common and least occurring LCRs in proteins. Our results show that though repeats of Gln are the most abundant but Asn repeats make longest stretch of low complexity. The results showed that potential of LCRs to form amyloids varies with their amino acid composition.

Item Type:	Journal Article
Publication:	PEERJ
Publisher:	PEERJ INC
Additional Information:	Copy right for this article belong to PEERJ INC
Keywords:	Low complexity regions; Amyloids; Amino acid runs; Functional annotation
Department/Centre:	Division of Biological Sciences > Centre for Neuroscience
Date Deposited:	22 Nov 2018 15:04
Last Modified:	25 Aug 2022 09:16
URI:	https://eprints.iisc.ac.in/id/eprint/61113

Actions (login required)

View Item