Microproteins transitioning into a new Phase: Defining the undefined

Recent advancements in omics technologies have unveiled a hitherto unknown group of short polypeptides called microproteins (miPs). Despite their size, accumulating evidence has demonstrated that miPs exert varied and potent biological functions. They act in paracrine, juxtracrine, and endocrine fas...

Full description

Saved in:

Bibliographic Details
Published in:	Methods (San Diego, Calif.) Vol. 220; pp. 38 - 54
Main Authors:	Sahgal, Aayushi, Uversky, Vladimir, Davé, Vrushank
Format:	Journal Article
Language:	English
Published:	United States 01-12-2023
Subjects:	Humans Intrinsically Disordered Proteins - chemistry Intrinsically Disordered Regions microProteins or microPeptides Liquid-Liquid Phase Separation Short open reading frames Cellular Processes and Diseases Membrane-less Organelles
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Recent advancements in omics technologies have unveiled a hitherto unknown group of short polypeptides called microproteins (miPs). Despite their size, accumulating evidence has demonstrated that miPs exert varied and potent biological functions. They act in paracrine, juxtracrine, and endocrine fashion, maintaining cellular physiology and driving diseases. The present study focuses on biochemical and biophysical analysis and characterization of twenty-four human miPs using distinct computational methods, including RIDAO, AlphaFold2, D P , FuzDrop, STRING, and Emboss Pep wheel. miPs often lack well-defined tertiary structures and may harbor intrinsically disordered regions (IDRs) that play pivotal roles in cellular functions. Our analyses define the physicochemical properties of an essential subset of miPs, elucidating their structural characteristics and demonstrating their propensity for driving or participating in liquid-liquid phase separation (LLPS) and intracellular condensate formation. Notably, miPs such as NoBody and pTUNAR revealed a high propensity for LLPS, implicating their potential involvement in forming membrane-less organelles (MLOs) during intracellular LLPS and condensate formation. The results of our study indicate that miPs have functionally profound implications in cellular compartmentalization and signaling processes essential for regulating normal cellular functions. Taken together, our methodological approach explains and highlights the biological importance of these miPs, providing a deeper understanding of the unusual structural landscape and functionality of these newly defined small proteins. Understanding their functions and biological behavior will aid in developing targeted therapies for diseases that involve miPs.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1046-2023 1095-9130
DOI:	10.1016/j.ymeth.2023.10.009