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Cited by 5Developmental Biology and Gene RegulationProtein Structure and DynamicsWnt/β-catenin signaling in development and cancer

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Modelling the structure of Short Gastrulation and generation of a toolkit for studying its function in Drosophila

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Frampton, Sophie L., Sutcliffe, Catherine, Baldock, Clair, Ashe, Hilary L.·2022·Biology Open
DOI 10.1242/bio.059199PMC PMC9194680

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Abstract

A BMP gradient is essential for patterning the dorsal-ventral axis of invertebrate and vertebrate embryos. The extracellular BMP binding protein Short Gastrulation (Sog) in Drosophila plays a key role in BMP gradient formation. In this study, we combine genome editing, structural and developmental approaches to study Sog function in Drosophila. We generate a sog knockout fly stock, which allows simple reintegration of altered versions of the sog coding sequence. As proof-of-principle, we test the requirement for two cysteine residues that were previously identified as targets for palmitoylation, which has been proposed to enhance Sog secretion. However, we show that the sogC27,28S mutant is viable with only very mild phenotypes, indicating that these residues and their potential modification are not critical for Sog secretion in vivo. Additionally, we use experimental negative stain EM imaging and hydrodynamic data to validate the AlphaFold structure prediction for Sog. The model suggests a more compact shape than the vertebrate ortholog Chordin and conformational flexibility between the C-terminal von Willebrand C domains. We discuss how this altered compactness may contribute to mechanistic differences in Sog and Chordin function during BMP gradient formation. This article has an associated First Person interview with the first author of the paper.

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Metadata

Authors
Frampton, S. L., Sutcliffe, C., Baldock, C., & Ashe, H. L.
Affiliations
  • University of Manchester (GB)
  • Manchester Academic Health Science Centre (GB)
Corresponding author
  • Baldock, Clair
  • Ashe, Hilary L.
ORCID
Venue
Biology Open
Publisher
The Company of Biologists
Published
2022-06-10
Volume
11
Issue
6
ISSN
2046-6390 (ISSN-L)
DOI
10.1242/bio.059199
PMC
PMC9194680
OpenAlex
W4281382514
Cited by
5
References
2
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1
FWCI
0.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Biology Open (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Biotechnology and Biological Sciences Research Council (BB/V008099/1, BB/M011208/1)
  • The University of Manchester
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
Keywords
short gastrulation, BMP gradient, dorsoventral patterning, Drosophila embryo, protein structure prediction, AlphaFold, cysteine palmitoylation, protein secretion, chordin, hydrodynamic characteristics, protein flexibility
MeSH terms
Animals, Drosophila, Humans, Signal Transduction, Bone Morphogenetic Proteins, Drosophila Proteins, Gastrulation

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