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Microproteins - discovery, structure and function
  • Jessica Mohsen,
  • Alina Martel,
  • Sarah Slavoff
Jessica Mohsen
Yale University
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Alina Martel
Yale University
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Sarah Slavoff
Yale University

Corresponding Author:[email protected]

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Advances in proteogenomic technologies have revealed hundreds to thousands of translated small open reading frames (sORFs) that encode microproteins in genomes across evolutionary space. While many microproteins have now been shown to play critical roles in biology and human disease, a majority of recently identified microproteins have little or no experimental evidence regarding their functionality. Computational tools have some limitations for analysis of short, poorly conserved microprotein sequences, so additional tools are needed to determine the role of each member of this recently discovered polypeptide class. A currently underexplored avenue in the study of microproteins is structure prediction and determination, which delivers a depth of functional information. In this review, we provide a brief overview of microprotein discovery methods, then examine examples of microprotein structures (and, conversely, intrinsic disorder) that have been experimentally determined using crystallography, cryo-electron microscopy, and NMR, which provide insight into their molecular functions and mechanisms. Additionally, we discuss examples of predicted microprotein structures that have provided insight or context regarding their function. Analysis of microprotein structure at the angstrom level, and confirmation of predicted structures, therefore, has potential to identify translated microproteins that are of biological importance and to provide molecular mechanism for their in vivo roles.
04 Jul 2023Submitted to PROTEOMICS
05 Jul 2023Submission Checks Completed
05 Jul 2023Assigned to Editor
05 Jul 2023Review(s) Completed, Editorial Evaluation Pending
05 Jul 2023Reviewer(s) Assigned
24 Jul 2023Editorial Decision: Revise Minor
03 Aug 2023Review(s) Completed, Editorial Evaluation Pending
03 Aug 20231st Revision Received
10 Aug 2023Editorial Decision: Accept