Dados do Trabalho

Título

Functional analysis of novel intrinsically disordered microproteins in Mycobacterium tuberculosis

Introdução

Open reading frames shorter than 100 codons (small ORFs - smORFs) are usually dismissed during genome annotation because of their high probability of being non-coding sequences. However, many microproteins encoded by smORFs were found to display important biological functions, highlighting the need to devise new ways to identify and study these small biological players. A proteogenomics approach can be applied to identify these smORFs accurately among the vast majority of spurious ORFs in this size range. To do so, we have previously developed a pipeline entitled Proteogenomic IdeNtification of Smorfs (µProteInS).

Objetivo (s)

Using this pipeline, we have detected novel smORFs in Mycobacterium tuberculosis. Many of the microproteins encoded by these novel smORFs showed intrinsically disordered domains, and such may present important biological roles.

Material e Métodos

Using µProteInS and InterPro, we have found 32 unannotated microproteins in M. tuberculosis with intrinsically disordered domains. We compared different software predictions for their physicochemical properties and structures with AlphaFold and other tools. Since proteomes show a tendency of conserving intrinsic disorder, we analyzed the degree of conservation using Blastp and Orthofinder, from which we obtained up to 382 homologous ORFs and 90 orthologous ORFs from different bacteria.

Resultados e Conclusão

These results show microproteins with intrinsic disorder can no longer be discarded in genome annotation. In the long-term, uncovering novel biological players in this pathogenic organism can also reveal novel targets for the development of drugs that could assist in the combat of multiresistant strains of M. tuberculosis, which is currently one of the main world’s public health challenges.

Palavras-chave

intrinsic disorder, tuberculosis, proteogenomics

Agradecimentos

This study was funded by National Institute of Science and Technology on Tuberculosis (INCT-TB), Brazil (Grant numbers: 489 421703–2017-2/17–1265-8/14.2.0914.1). CB (310344/2016–6), PM (305203/2018–5) and LB (520182/99–5) are research career awardees of the National Council for Scientific and Technological Development of Brazil (CNPq). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.