Target highlights in CASP13: Experimental target structures through the eyes of their authors

Lepore, Rosalba; Kryshtafovych, Andriy; Alahuhta, Markus; Verasztó, Harshul Arora; Bomble, Yannick J.; Bufton, J.C.; Bullock, Alex N.; Caba, Cody; Cao, Heidi B.; Davies, Owen R.; Desfosses, Ambroise; Dunne, Matthew; Fidelis, Krzysztof; Goulding, Celia W.; Gurusaran, Manickam; Gutsche, Irina; Harding, Christopher John; Hartmann, M.D.; Hayes, Christopher S.; Joachimiak, A.; Leiman, P.G.; Loppnau, P.; Lovering, Andrew L.; Лунин, В.В.; Michalska, K.; Mir-Sanchis, Ignacio; Mitra, Alok K.; Moult, John; Phillips, George N.; Pinkas, Daniel; Rice, Phoebe A.; Tong, Yufeng; Topf, Maya; Walton, Jonathan D.; Schwede, Torsten

doi:10.1002/prot.25805

Cited by 12 publications

(21 citation statements)

References 104 publications

(229 reference statements)

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“…Although the results in terms of more accurate models are not impressive, it is clear that much more development is possible, and we have already seen several groups introduce methods specifically tailored to particular data types. CASP continues to investigate the best ways of assessing how effectively functional information can be derived from models, and in this round, solicited assessment comments from those who provided the prediction targets . An interesting development during CASP13 was the introduction of a CASP commons experiment (http://predictioncenter.org/caspcommons/).…”

Section: Discussionmentioning

confidence: 99%

“…CASP continues to investigate the best ways of assessing how effectively functional information can be derived from models, 42,43 and in this round, solicited assessment comments from those who provided the prediction targets. 44 An interesting development during CASP13 was the introduction of a CASP commons experiment (http:// predictioncenter.org/caspcommons/). Biologists were canvased to identify a total of 35 small proteins for which structure would be particularly useful for their research.…”

Section: Discussionmentioning

confidence: 99%

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Critical assessment of methods of protein structure prediction (CASP)—Round XIII

et al. 2019

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CASP (critical assessment of structure prediction) assesses the state of the art in modeling protein structure from amino acid sequence. The most recent experiment (CASP13 held in 2018) saw dramatic progress in structure modeling without use of structural templates (historically “ab initio” modeling). Progress was driven by the successful application of deep learning techniques to predict inter‐residue distances. In turn, these results drove dramatic improvements in three‐dimensional structure accuracy: With the proviso that there are an adequate number of sequences known for the protein family, the new methods essentially solve the long‐standing problem of predicting the fold topology of monomeric proteins. Further, the number of sequences required in the alignment has fallen substantially. There is also substantial improvement in the accuracy of template‐based models. Other areas—model refinement, accuracy estimation, and the structure of protein assemblies—have again yielded interesting results. CASP13 placed increased emphasis on the use of sparse data together with modeling and chemical crosslinking, SAXS, and NMR all yielded more mature results. This paper summarizes the key outcomes of CASP13. The special issue of PROTEINS contains papers describing the CASP13 assessments in each modeling category and contributions from the participants.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Critical assessment of methods of protein structure prediction (CASP)—Round XIII

et al. 2019

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“…Our previous model was critical in designing mutations and experiments that ultimately resulted in the high-resolution structures presented herein. Nevertheless, this highlights the continued need for high-resolution experimental structure determination, particularly in the case of coiled-coil and hetero-oligomeric structures, which remain beyond the reaches of in silico structure prediction methods, despite advances in our understanding of protein folding and the increasing accuracy in predicting novel folds of monomers and homo-oligomers (Lepore et al, 2019, Callaway, 2020).…”

Section: Discussionmentioning

confidence: 99%

Structural basis of meiotic chromosome synaptic elongation through hierarchical fibrous assembly of SYCE2-TEX12

Dunce

Salmon

Davies

2020

Preprint

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The supramolecular structure of the synaptonemal complex (SC) mediates homologous chromosome synapsis and facilitates the formation of genetic crossovers during meiosis. The mammalian SC is formed of eight coiled-coil proteins which interact in specific subcomplexes and self-assemble into distinct macromolecular arrays that fulfil specific aspects of the SC’s dynamic functional architecture. Here, we report the structure of SC subcomplex SYCE2-TEX12 and its mechanism of self-assembly into fibres that define the SC’s midline longitudinal structure. X-ray crystal structures, electron microscopy, biophysical and mutational analyses reveal that SYCE2-TEX12 is assembled from 2:2 complexes in which TEX12 chains are positioned at either end of a rod-like SYCE2 dimer. These molecular building-blocks assemble laterally into 4:4 complexes, and longitudinally into fibres of potentially limitless length, which acts as string-like threads that wind around one another in intertwined fibres of up to 40-nm in width and several micrometres in length. This hierarchical assembly mechanism is reminiscent of intermediate filament proteins and results in SYCE2-TEX12 fibres that can span the entire chromosome length, thereby providing the underpinning structural support for SC elongation during meiotic chromosome synapsis.

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“…The T1 domain binds to the GABA B2 subunit, while the H1 domain binds to the Gβ subunit of the guanine nucleotide-binding protein (G-protein) ( Schwenk et al, 2010 ; Turecek et al, 2014 ; Zheng et al, 2019 ). X-ray crystallography of the T1 and H1 domains of KCTD12 and KCTD16 ( Lepore et al, 2019 ; Zheng et al, 2019 ; Zuo et al, 2019 ) revealed that the secondary and tertiary protein structures of those domains are highly conserved in the KCTD proteins. However, the T1 domain possesses a highly divergent loop between helix α2 and strand β3 (following the nomenclature from Zuo et al, 2019 ), while the H1 domain features a divergent loop between the strands β4 and β5 (following the nomenclature from Zheng et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals

Bhandari

Vandael

Fernández-Fernández

et al. 2021

eLife

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The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors, and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation.

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Target highlights in CASP13: Experimental target structures through the eyes of their authors

Cited by 12 publications

References 104 publications

Critical assessment of methods of protein structure prediction (CASP)—Round XIII

Critical assessment of methods of protein structure prediction (CASP)—Round XIII

Structural basis of meiotic chromosome synaptic elongation through hierarchical fibrous assembly of SYCE2-TEX12

GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals

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