iLIR@viral: A web resource for LIR motif-containing proteins in viruses

Jacomin, Anne-Claire; Samavedam, Siva; Charles, Hannah; Nezis, Ioannis P.

doi:10.1080/15548627.2017.1356978

Cited by 23 publications

(18 citation statements)

References 78 publications

(114 reference statements)

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“…Notably, a database of viral proteins from over 16000 viral sequences and 2500 viral species, revealed a large number of potential LIR sequences contained within the viral proteins [ 99 ]. For example, a potential LIR was identified in the HIV-1 protein Nef which has previously been shown to inhibit autophagosome maturation and to colocalize with LC3 and BECN1 to protect HIV-1 from autophagy-mediated clearance [ 100 , 101 ].…”

Section: Mimicking the Lir To Subvert Host Machinerymentioning

confidence: 99%

Host–pathogen interactions and subversion of autophagy

McEwan

2017

Essays in Biochemistry

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Macroautophagy (‘autophagy’), is the process by which cells can form a double-membraned vesicle that encapsulates material to be degraded by the lysosome. This can include complex structures such as damaged mitochondria, peroxisomes, protein aggregates and large swathes of cytoplasm that can not be processed efficiently by other means of degradation. Recycling of amino acids and lipids through autophagy allows the cell to form intracellular pools that aid survival during periods of stress, including growth factor deprivation, amino acid starvation or a depleted oxygen supply. One of the major functions of autophagy that has emerged over the last decade is its importance as a safeguard against infection. The ability of autophagy to selectively target intracellular pathogens for destruction is now regarded as a key aspect of the innate immune response. However, pathogens have evolved mechanisms to either evade or reconfigure the autophagy pathway for their own survival. Understanding how pathogens interact with and manipulate the host autophagy pathway will hopefully provide a basis for combating infection and increase our understanding of the role and regulation of autophagy. Herein, we will discuss how the host cell can identify and target invading pathogens and how pathogens have adapted in order to evade destruction by the host cell. In particular, we will focus on interactions between the mammalian autophagy gene 8 (ATG8) proteins and the host and pathogen effector proteins.

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Section: Mimicking the Lir To Subvert Host Machinerymentioning

confidence: 99%

Host–pathogen interactions and subversion of autophagy

McEwan

2017

Essays in Biochemistry

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“…While algorithmic approaches seek to identify a broad range of SLiM types, more specialized resources have emerged to track the distribution of a particular SLiM in viral proteins. For example, iLIR@viral is a web resource dedicated to detecting LIR motif-containing proteins in viruses [59]. LC3interacting regions (LIR motifs) are SLiMs that mediate protein-protein interactions involved in autophagy, as used by influenza A virus M2 protein to subvert autophagy and maintain virion stability [60].…”

Section: Motif-specific Databasesmentioning

confidence: 99%

Resources to Discover and Use Short Linear Motifs in Viral Proteins

Hraber

O’Maille

Silberfarb

et al. 2020

Trends in Biotechnology

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Viral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Motif mimicry tolerates mutations, evolves quickly to modify interactions with the host, and enables modular interactions with protein complexes. Host cells cannot easily coordinate changes to conserved motif recognition and binding interfaces under selective pressure to maintain critical signaling pathways. SLiMs offer potential for use in synthetic biology, such as better immunogens and therapies, but may also present biosecurity challenges. We survey viral uses of SLiMs to mimic host proteins, and information resources available for motif discovery. As the number of examples continues to grow, knowledge management tools are essential to help organize and compare new findings.

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“…The interaction between mammalian ATG8s and LIR containing proteins serves to control all aspects of the autophagy pathway, from cargo selection to formation, transport and fusion of the autophagosome. Not only are these interactions sequences present in mammalian, plant, fungi and invertebrate species, they are also present in a number of viral [41] and bacterial [42] proteins, potentially to aid pathogen survival and subversion of the pathway. We have identified a highly conserved LIR within both ATG2A and ATG2B that differ only in a few amino acids both N-and C-terminal of the core LIR sequence (FCIL; Figure 2D).…”

Section: Identification Of a Conserved Lc3 Interaction Region Sequencmentioning

confidence: 99%

A conserved ATG2-GABARAP interaction is critical for phagophore closure

Božić

Bekerom

Milne

et al. 2019

Preprint

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The intracellular trafficking pathway, macroautophagy, acts as a recycling and disposal service that can be upregulated during periods of stress, to maintain cellular homeostasis.An essential transition point in the pathway is the sealing of the immature phagophore to form an autophagosome, isolating unwanted cargo prior to lysosomal degradation. However, little mechanistic detail is known about phagophore closure. Human ATG2A and ATG2B proteins, through their interaction with WIPI proteins, are thought to be key players during phagophore closure. We have identified a highly-conserved motif driving the interaction between human ATG2 and GABARAP proteins that is in close proximity to the ATG2-WIPI4 interaction site. We show that the ATG2-GABARAP interaction mutants are unable to close phagophores resulting in blocked autophagy, similar to ATG2A/ATG2B double knock-out cells. In contrast, the ATG2-WIPI4 interaction mutant fully restored phagophore closure and autophagy flux, similar to wild type ATG2. Taken together, we provide new mechanistic insights to the requirements for ATG2 function at the phagophore and suggest that an ATG2-GABARAP interaction is essential for phagophore closure, whereas ATG2-WIPI4 interaction is dispensable. Abbreviations: ATG2 -Autophagy-related protein 2; ESCRT -endosomal sorting complex required for transport; GABARAP -Gamma-aminobutyric acid receptor-associated protein: GIM -GABARAP Interaction Motif; GST -Glutathione S-transferase; LIR -LC3 interaction region; MAP1LC3 (LC3) -Microtubule-associated proteins 1A/1B light chain; PtIns3Pphosphatidylinositol-3-phosphate; PI3K -PtsIns3P kinase; SQSTM1 -Sequestosome-1; VPS34 -Vacuolar Protein sorting 34; WIPI -WD repeat domain phosphoinositide-interacting protein;

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iLIR@viral: A web resource for LIR motif-containing proteins in viruses

Cited by 23 publications

References 78 publications

Host–pathogen interactions and subversion of autophagy

Host–pathogen interactions and subversion of autophagy

Resources to Discover and Use Short Linear Motifs in Viral Proteins

A conserved ATG2-GABARAP interaction is critical for phagophore closure

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