Ali, M., Nicieza, A., Wootton, R. J. (2003). Compensatory growth in fishes: a response to growth depression. ? Fish and Fisheries, 4, (2), 147-190. Sponsorship: Royal Society of London ? Chinese Academy of Sciences Exchange awardCompensatory growth (CG) is a phase of accelerated growth when favourable conditions are restored after a period of growth depression. CG reduces variance in size by causing growth trajectories to converge and is important to fisheries management, aquaculture and life history analysis because it can offset the effects of growth arrests. Compensatory growth has been demonstrated in both individually housed and grouped fish, typically after growth depression has been induced by complete or partial food deprivation. Partial, full and over-compensation have all been evoked in fish, although over-compensation has only been demonstrated when cycles of deprivation and satiation feeding have been imposed. Individually housed fish have shown that CG is partly a response to hyperphagia when rates of food consumption are significantly higher than those in fish that have not experienced growth depression. The severity of the growth depression increases the duration of the hyperphagic phase rather than maximum daily feeding rate. In many studies, growth efficiencies were higher during CG. Changes in metabolic rate and swimming activity have not been demonstrated yet to play a role. Periods of food deprivation induce changes in the storage reserves, particularly lipids, of fish. Apart from the strong evidence for the restoration of somatic growth trajectories, CG is a response to restore lipid levels. Although several neuro-peptides, including neuropeptide-Y, are probably involved in the control of appetite, their role and the role of hormones, such as growth hormone (GH) and insulin-like growth factor (IGF), in the hyperphagia associated with CG are still unclear. The advantages of CG probably relate to size dependencies of mortality, fecundity and diet that are characteristic of teleosts. These size dependencies favour a recovery from the effects of growth depression if environmental factors allow. High growth rates may also impose costs, including adverse effects on future development, growth, reproduction and swimming performance. Hyperphagia may lead to riskier behaviour in the presence of predators. CG's evolutionary consequences are largely unexplored. An understanding of why animals grow at rates below their physiological capacity, an evaluation of the costs of rapid growth and the identification of the constraints on growth trajectories represent major challenges for life-history theory.Peer reviewe

Specific protein–protein interactions are central to all processes that underlie cell physiology. Numerous studies have together identified hundreds of thousands of human protein–protein interactions. However, many interactions remain to be discovered, and low affinity, conditional, and cell type‐specific interactions are likely to be disproportionately underrepresented. Here, we describe an optimized proteomic peptide‐phage display library that tiles all disordered regions of the human proteome and allows the screening of ~ 1,000,000 overlapping peptides in a single binding assay. We define guidelines for processing, filtering, and ranking the results and provide PepTools, a toolkit to annotate the identified hits. We uncovered >2,000 interaction pairs for 35 known short linear motif (SLiM)‐binding domains and confirmed the quality of the produced data by complementary biophysical or cell‐based assays. Finally, we show how the amino acid resolution‐binding site information can be used to pinpoint functionally important disease mutations and phosphorylation events in intrinsically disordered regions of the proteome. The optimized human disorderome library paired with PepTools represents a powerful pipeline for unbiased proteome‐wide discovery of SLiM‐based interactions.

The spike protein of SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on the host cell surface and subsequently enters host cells through receptor-mediated endocytosis. Additional cell receptors may be directly or indirectly involved, including integrins. The cytoplasmic tails of ACE2 and integrins contain several predicted short linear motifs (SLiMs) that may facilitate internalization of the virus as well as its subsequent propagation through processes such as autophagy. Here, we measured the binding affinity of predicted interactions between SLiMs in the cytoplasmic tails of ACE2 and integrin β3 with proteins that mediate endocytic trafficking and autophagy. We validated that a class I PDZ-binding motif mediated binding of ACE2 to the scaffolding proteins SNX27, NHERF3, and SHANK, and that a binding site for the clathrin adaptor AP2 μ2 in ACE2 overlaps with a phospho-dependent binding site for the SH2 domains of Src family tyrosine kinases. Furthermore, we validated that an LC3-interacting region (LIR) in integrin β3 bound to the ATG8 domains of the autophagy receptors MAP1LC3 and GABARAP in a manner enhanced by LIR-adjacent phosphorylation. Our results provide molecular links between cell receptors and mediators of endocytosis and autophagy that may facilitate viral entry and propagation.

A key function of reversible protein phosphorylation is to regulate protein–protein interactions, many of which involve short linear motifs (3–12 amino acids). Motif‐based interactions are difficult to capture because of their often low‐to‐moderate affinities. Here, we describe phosphomimetic proteomic peptide‐phage display, a powerful method for simultaneously finding motif‐based interaction and pinpointing phosphorylation switches. We computationally designed an oligonucleotide library encoding human C‐terminal peptides containing known or predicted Ser/Thr phosphosites and phosphomimetic variants thereof. We incorporated these oligonucleotides into a phage library and screened the PDZ (PSD‐95/Dlg/ZO‐1) domains of Scribble and DLG1 for interactions potentially enabled or disabled by ligand phosphorylation. We identified known and novel binders and characterized selected interactions through microscale thermophoresis, isothermal titration calorimetry, and NMR. We uncover site‐specific phospho‐regulation of PDZ domain interactions, provide a structural framework for how PDZ domains accomplish phosphopeptide binding, and discuss ligand phosphorylation as a switching mechanism of PDZ domain interactions. The approach is readily scalable and can be used to explore the potential phospho‐regulation of motif‐based interactions on a large scale.

Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a viral peptide discovery approach covering 23 coronavirus strains that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction dampened SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.