The RNA Interference Effector Protein Argonaute 2 Functions as a Restriction Factor Against SARS-CoV-2

López-Orozco, Joaquín; Fayad, Nawell; Khan, Juveriya Q; Felix-Lopez, Alberto; Elaish, Mohamed; Rohamare, Megha; Sharma, Mehar Chand; Falzarano, Darryl; Wilson, Joyce A.; Hobman, Tom C.; Kumar, Anil

doi:10.1016/j.jmb.2023.168170

Cited by 6 publications

(2 citation statements)

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“…Hence, it appears that each AGO protein harbors distinguishing features ranging from its coding gene to its protein function. However, research into these differentiation points often encounters challenges, yielding contradictory findings, such as the antiviral activity of AGO2 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 12 and the lack of it against other viruses 13 .…”

Section: Introductionmentioning

confidence: 99%

“…Another relevant example of functional differentiation is the prokaryotic AGOs which are divided into two groups based on the possession of a PAZ domain, that associates with nucleolytic activity 17 . In humans, AGOs are characterized by both subfuctionalization and the recently discovered neofunctionalization 8,12,[18][19][20] . Evolution either strongly conserves structural parts of a protein to preserve its functions or introduces variability in the type/chemical property of a specific amino-acid leading to functional divergence 21 .…”

Section: Introductionmentioning

confidence: 99%

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Comparative structural insights and functional analysis for the distinct unbound states of Human AGO proteins

Kakoulidis,

Theotoki,

Pantazopoulou

et al. 2024

Preprint

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The four human Argonaute (AGO) proteins, essential in RNA interference and gene regulation, exhibit high sequence and structural similarity, yet differ functionally. Our molecular dynamics simulations revealed that while AGO proteins adopt similar open-close states, each one displays distinct local conformations, leading to unique interdomain distances and intramolecular interactions. We found that GW182/ZSWIM8 interaction sites, catalytic/pseudo-catalytic tetrads and long common protein subsequences conserve their molecular movement with minute differences but have varying solvent accessibility per AGO. We observed diverse stability patterns at the post-transcriptional sites of the AGOs, except for AGO4. Combining simulation data with large datasets of experimental structures and AlphaFold’s predictions, we identified proteins with gene sequence and protein structure similarities that operate in the mitosis pathway and share mitosis-related interactors and miRNA targets. Additionally, we suggest a zinc ion binding function in AGO proteins, predicting potential binding sites and detecting structurally similar proteins with the same function.

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Section: Introductionmentioning

confidence: 99%