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Structural basis for binding of Drosophila Smaug to the GPCR smoothened and to the germline inducer Oskar

Drosophila Smaug and its orthologs comprise a family of mRNA repressor proteins that exhibit various functions during animal development. Smaug proteins contain a characteristic RNA-binding sterile-α motif (SAM) domain and a conserved but uncharacterized N-terminal domain (NTD). Here, we resolved th...

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Bibliographic Details
Main Authors: Kubíková, Jana (Author) , Ubartaitė, Gabrielė (Author) , Metz, Jutta (Author) , Jeske, Mandy (Author)
Format: Article (Journal)
Language:English
Published: July 31, 2023
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2023, Volume: 120, Issue: 32, Pages: 1-11
ISSN:1091-6490
DOI:10.1073/pnas.2304385120
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1073/pnas.2304385120
Verlag, kostenfrei, Volltext: https://www.pnas.org/doi/10.1073/pnas.2304385120
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Author Notes:Jana Kubíková, Gabrielė Ubartaitė, Jutta Metz, and Mandy Jeske
Description
Summary:Drosophila Smaug and its orthologs comprise a family of mRNA repressor proteins that exhibit various functions during animal development. Smaug proteins contain a characteristic RNA-binding sterile-α motif (SAM) domain and a conserved but uncharacterized N-terminal domain (NTD). Here, we resolved the crystal structure of the NTD of the human SAM domain-containing protein 4A (SAMD4A, a.k.a. Smaug1) to 1.6 Å resolution, which revealed its composition of a homodimerization D subdomain and a subdomain with similarity to a pseudo-HEAT-repeat analogous topology (PHAT) domain. Furthermore, we show that Drosophila Smaug directly interacts with the Drosophila germline inducer Oskar and with the Hedgehog signaling transducer Smoothened through its NTD. We determined the crystal structure of the NTD of Smaug in complex with a Smoothened α-helical peptide to 2.0 Å resolution. The peptide binds within a groove that is formed by both the D and PHAT subdomains. Structural modeling supported by experimental data suggested that an α-helix within the disordered region of Oskar binds to the NTD of Smaug in a mode similar to Smoothened. Together, our data uncover the NTD of Smaug as a peptide-binding domain.
Item Description:Gesehen am 16.01.2024
Physical Description:Online Resource
ISSN:1091-6490
DOI:10.1073/pnas.2304385120

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