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. 2021 Sep 8;8:725072. doi: 10.3389/fmed.2021.725072

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Copyright © 2021 De Meyer, Fijalkowski, Jonckheere, De Sutter, Eyckerman and Van Damme.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Model of SspH2 resulting in SUGT1-dependent NOD1 signaling at the dynamic actin cytoskeleton. SspH2 is localized to the plasma membrane (PM) by S-palmitoylation (dark blue zigzag line). Subsequent interaction with profilins (PFN1 and −2) specifies the localization of effector SspH2 further toward polymerizing actin filaments as a result of profilin binding to proline-rich regions (PRRs) of formin(-like) proteins (yellow), such as DIAPH1 and FMNL2. Barbed ends of actin filaments are bound to formins through formin-homology domains (FH2). SspH2 localized at the actin cytoskeleton allows for NOD1 signaling upon SUGT1 binding and E3 ubiquitin ligase activation. Proteins in greyscale represent proteins that were not (significantly) enriched as SspH2 interactors using Virotrap. Interactors in shades of blue were previously reported and significantly enriched in the Gag-SspH2 Virotrap samples.