A helical LC3-interacting region mediates the interaction between the retroviral restriction factor Trim5α and mammalian autophagy-related ATG8 proteins
© 2018 Keown et al. The retroviral restriction factor tripartite motif-containing 5α (Trim5α) acts during the early postentry stages of the retroviral life cycle to block infection by a broad range of retroviruses, disrupting reverse transcription and integration. The mechanism of this restriction is poorly understood, but it has recently been suggested to involve recruitment of components of the autophagy machinery, including members of the mammalian autophagy-related 8 (ATG8) family involved in targeting proteins to the autophagosome. To better understand the molecular details of this interaction, here we utilized analytical ultracentrifugation to characterize the binding of six ATG8 isoforms and determined the crystal structure of the Trim5α Bbox coiled-coil region in complex with one member of the mammalian ATG8 proteins, autophagy-related protein LC3 B (LC3B). We found that Trim5α binds all mammalian ATG8s and that, unlike the typical LC3-interacting region (LIR) that binds to mammalian ATG8s through a β-strand motif comprising approximately six residues, LC3B binds to Trim5α via the α-helical coiled-coil region. The orientation of the structure demonstrated that LC3B could be accommodated within a Trim5α assembly that can bind the retroviral capsid. However, mutation of the binding interface does not affect retroviral restriction. Comparison of the typical linear β-strand LIR with our atypical helical LIR reveals a conservation of the presentation of residues that are required for the interaction with LC3B. This observation expands the range of LC3B-binding proteins to include helical binding motifs and demonstrates a link between Trim5α and components of the autophagosome.
Showing items related by title, author, creator and subject.
Laminar flow devices for the measurement of diffusional coefficients of proteins and protein complexes Nock, V.; Nivaskumar, M.; Dobson, R. (University of Canterbury. Electrical and Computer EngineeringUniversity of Canterbury. Biomolecular Interaction Centre, 2015)
Effects of milk minerals and proteins on fouling and cleaning of polyamide reverse osmosis membranes Tew, X.W.; Morison, K.R. (University of Canterbury. Chemical and Process Engineering, 2014)Reverse osmosis is used for the concentration of milk to reduce transportation costs from farms, and also within dairy factories to concentrate dairy liquids. A SEPA flat sheet reverse osmosis apparatus with a polyamide ...
Lassé, Moritz (University of Canterbury. School of Biological Sciences, 2013)This thesis explores the complex relationship between food protein structure and digestibility. Food proteins are important nutrients that play a central role in controlling the textural properties of many foods. Processing ...