CoCoNat: a novel method based on deep learning for coiled-coil prediction

Madeo, Giovanni; Savojardo, Castrense; Manfredi, Matteo; Martelli, Pier Luigi; Casadio, Rita

doi:10.1093/bioinformatics/btad495

Cited by 9 publications

(5 citation statements)

References 34 publications

(75 reference statements)

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“…12,29 The predicted structures of Daed and Gasz showed that the second of the two α-helixes (Ala191– His235) of Daed roughly overlaps with the CC domain (Thr206–Ser234) and that the two α-helixes in Gasz (Phe345–Glu374 and Glu383–Ser412) are present between the SAM and TM domains (Figure 1C). The amino acid sequence-based prediction of the CC region 32 also roughly overlaps with the tandem α-helix regions (Figure S1A), supporting the AlphaFold2 prediction. We propose that the two tandem α-helixes present in both Gasz and Daed are referred to as extended coiled-coil (eCC) domains (Figure 1C).…”

Section: Resultssupporting

confidence: 67%

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Diptera-specific Daedalus controls Zucchini endonucleolysis in piRNA biogenesis independent of exonucleases

Koga,

Hirakata,

Negishi

et al. 2024

Preprint

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SummarypiRNAs protect germline genomes and maintain fertility by repressing transposons. Daedalus and Gasz act together as a mitochondrial scaffold for Armitage, a necessary factor for Zucchini-dependent piRNA processing. However, the mechanism underlying this function remains unclear. Here, we find that the roles of Daedalus and Gasz in this process are distinct, although both are necessary: Daedalus physically interacts with Armitage, whereas Gasz supports Daedalus to maintain its function. Daedalus binds to Armitage through two distinct regions, an extended coiled-coil identified in this study, and a SAM. The former tethers Armitage to mitochondria, while the latter controls Zucchini endonucleolysis to define the length of piRNAs in an exonuclease-independent manner. piRNAs produced in the absence of Daedalus SAM do not exhibit full transposon silencing functionality. Daedalus is Diptera specific. UnlikeDrosophilaand mosquitoes, evolutionarily more complex species, such as mice, rely on exonucleases after Zucchini processing to specify the length of piRNAs.

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Section: Resultssupporting

confidence: 67%

“…( A ) Sequence-based CC prediction of Daed (upper) and Gasz (lower) by CoCoNat. 32 Red line indicates the CC region predicted by AlphaFold2. ( B ) Western blotting shows that anti-Daed monoclonal antibodies produced in this study are specific to Daed.…”

Section: Supplemental Figure Legendsmentioning

confidence: 99%

Diptera-specific Daedalus controls Zucchini endonucleolysis in piRNA biogenesis independent of exonucleases

Koga,

Hirakata,

Negishi

et al. 2024

Preprint

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“…2 ). According to 3 in silico coiled-coil structure prediction tools (CoCoNat, DeepCoil2, and CoCoPred) 33 – 35 , the variant was consistently predicted to disrupt the coiled-coil structure in CARD9 and thus be pathogenic (Supplementary Fig. 4 ).…”

Section: Resultsmentioning

confidence: 99%

Increased susceptibility to Mycobacterium avium complex infection in miniature Schnauzer dogs caused by a codon deletion in CARD9

Mizukami,

Dorsey-Oresto,

Raj

et al. 2024

Sci Rep

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Mammals are generally resistant to Mycobacterium avium complex (MAC) infections. We report here on a primary immunodeficiency disorder causing increased susceptibility to MAC infections in a canine breed. Adult Miniature Schnauzers developing progressive systemic MAC infections were related to a common founder, and pedigree analysis was consistent with an autosomal recessive trait. A genome-wide association study and homozygosity mapping using 8 infected, 9 non-infected relatives, and 160 control Miniature Schnauzers detected an associated region on chromosome 9. Whole genome sequencing of 2 MAC-infected dogs identified a codon deletion in the CARD9 gene (c.493_495del; p.Lys165del). Genotyping of Miniature Schnauzers revealed the presence of this mutant CARD9 allele worldwide, and all tested MAC-infected dogs were homozygous mutants. Peripheral blood mononuclear cells from a dog homozygous for the CARD9 variant exhibited a dysfunctional CARD9 protein with impaired TNF-α production upon stimulation with the fungal polysaccharide β-glucan that activates the CARD9-coupled C-type lectin receptor, Dectin-1. While CARD9-deficient knockout mice are susceptible to experimental challenges by fungi and mycobacteria, Miniature Schnauzer dogs with systemic MAC susceptibility represent the first spontaneous animal model of CARD9 deficiency, which will help to further elucidate host defense mechanisms against mycobacteria and fungi and assess potential therapies for animals and humans.

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“…although this was not apparent at the CASP15 experiment (Simpkin, Mesdaghi et al, 2023). Also notable are the continued difficulties with coiled-coil proteins, whose unpredictable irregularities, oligomeric state and parallel vs antiparallel architectures remain, despite ongoing efforts (Madeo et al, 2023;Madaj et al, 2024), a significant hindrance to structure prediction and hence the use of modelled structures for MR.…”

Section: Discussionmentioning

confidence: 99%

In the AlphaFold era, when is experimental phasing of protein crystals still required?

Keegan,

Simpkin,

Rigden

2024

Preprint

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The availability of highly accurate protein structure predictions from AlphaFold 2 (AF2) and similar tools has hugely expanded the applicability of Molecular Replacement (MR) for crystal structure solution. Many structures solve routinely using raw models, structures processed to remove unreliable parts or models split into distinct structural units. There is therefore an open question around how many and which cases still require experimental phasing methods such as single-wavelength anomalous diffraction (SAD). Here we address the question using a large set of PDB deposits that were solved by SAD. A large majority (87%) solve using unedited or minimally edited AF2 predictions. A further 17 (4%) yield straightforwardly to MR after splitting of the AF2 prediction using Slice’N’Dice, although different splitting methods succeed on slightly different sets of cases. We also find that further unique targets can be solved by alternative modelling approaches such as ESMFold (four cases), alternative MR approaches such as ARCIMBOLDO and AMPLE (two cases each), and multimeric model building with AlphaFold-Multimer or UniFold (three cases). Ultimately, only 12 cases, or 3% of the SAD-phased set did not yield to any form of MR tested here, offering valuable hints as to the number and characteristics of cases where experimental phasing remains essential for macromolecular structure solution.

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CoCoNat: a novel method based on deep learning for coiled-coil prediction

Cited by 9 publications

References 34 publications

Diptera-specific Daedalus controls Zucchini endonucleolysis in piRNA biogenesis independent of exonucleases

Diptera-specific Daedalus controls Zucchini endonucleolysis in piRNA biogenesis independent of exonucleases

Increased susceptibility to Mycobacterium avium complex infection in miniature Schnauzer dogs caused by a codon deletion in CARD9

In the AlphaFold era, when is experimental phasing of protein crystals still required?

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