Journal: bioRxiv

Article Title: Feather keratin in Pavo cristatus : A tentative structure

doi: 10.1101/2024.09.08.611866

Figure Lengend Snippet: AlphaFold prediction of most parsimonious tentative structure of the F-keratin tetrameric N-block, AA 1-–52 (4 × 52 = 208 residues). Monomers are color-coded by chain (blue, red, green, yellow). Cysteine residues are displayed in a ball-stick view with standard colors. (a) Side view, staircase arrangement of helical β -strands in levels 1-8 (highlighted in the colors of adjacent β -strands) in the axial direction. Chain orientations of individual monomers are indicated by the respective AA number. (b) side view 90° turned, β -strands are rotationally staggered by an average horizontal angle of 11.125°per β -strand. The 8th strand is rotated 89°against the 1st strand in Pavo cristatus . The distance between the sandwiched sheets is 1.0-1.2 nm. Note that the polypeptide backbones of the four monomers are intertwined between strands in levels 4 and 5. (c) Axial view. (d) Equatorial cross-section of (a), corresponding to (c). AA 37-S, 38-T, and 47-I sit in the equatorial plane.

Article Snippet: So far, according to AlphaFold models, C-block segments of Gallus gallus and Larus novaehollandiae lack such interfacial fit.

Techniques: Blocking Assay

Journal: bioRxiv

Article Title: Feather keratin in Pavo cristatus : A tentative structure

doi: 10.1101/2024.09.08.611866

Figure Lengend Snippet: AlphaFold prediction of the Pavo cristatus F-keratin tetrameric C-block, AA 81-–100 (4 × 20 = 80 residues). Monomers are color-coded by chain (blue, red, green, yellow). The four 98-Y and 12 cysteine residues are displayed in a ball-stick view with standard colors. Chain orientations of individual monomers are indicated by the respective amino acid number. (a) Side view, filament axis vertical. (b) The side view turned 90°around the filament axis. (c) Top view, along the filament axis. Note that each pair of β -strands forms one level; the arrangement is rectangular rather than square in the (x,y) plane. The direction of the β -strand arrows is from N-to C-terminus. (d) shows the outer aromates from the 81-FGYGFGGLGCF motif in the same view as (b).

Article Snippet: So far, according to AlphaFold models, C-block segments of Gallus gallus and Larus novaehollandiae lack such interfacial fit.

Techniques: Blocking Assay

Journal: BMC Medical Genomics

Article Title: Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy

doi: 10.1186/s12920-023-01780-9

Figure Lengend Snippet: The MED12 pathogenic variant is responsible for dilated cardiomyopathy (DCM). (A) The image presents the pedigree of the family with DCM. Variant carriers: black; relatives without the variant: white; slashed line: the deceased member; square: male; circle: female; arrow: proband; triangle: spontaneous abortion. (B) The cardiac magnetic resonance imaging image (CMR) presents dilated cardiomyopathy in the index patient. (C) Direct Sanger-sequencing chromatograms show the MED12 variant sequence in the father, the mother, and the DCM-affected son. The arrow shows the nucleotide position of G/A in the wild-type homozygous father, the heterozygous mother, and the hemizygous patient. (D) The CLUSTALW server was used to compare the alignment of MED12 residues among various MED12 orthologs. The valine amino acids are shown in box

Article Snippet: Since it was impossible to model a huge MED12 protein with AlphaFold2 ( https://colab.research.google.com/github/sokrypton/ColabFold/blob/main/AlphaFold2.ipynb ) methods [ ], the InterPro ( https://www.ebi.ac.uk/interpro/ ) web server [ ] was first employed to identify and select the desired domains of the MED12 protein according to the study of Klatt, et al. [ ].

Techniques: Variant Assay, Magnetic Resonance Imaging, Sequencing

Journal: BMC Medical Genomics

Article Title: Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy

doi: 10.1186/s12920-023-01780-9

Figure Lengend Snippet: The image depicts the structural prediction of the MED12 protein. (A) The image presents the domain prediction, performed with the InterPro web server. (B) The computational model of the normal MED12 protein constructed with the aid of the AlphaFold2 web server is presented herein. The surface yellow color shows the normal amino acid. (C) The computational model of the variant MED12 protein constructed with the use of the AlphaFold2 web server is presented herein. The surface green color shows the variant amino acid. (D) Superimposed AlphaFold2 models of MED12 (amino acid 1–800) as normal (green), Val417Ile (pink)

Article Snippet: Since it was impossible to model a huge MED12 protein with AlphaFold2 ( https://colab.research.google.com/github/sokrypton/ColabFold/blob/main/AlphaFold2.ipynb ) methods [ ], the InterPro ( https://www.ebi.ac.uk/interpro/ ) web server [ ] was first employed to identify and select the desired domains of the MED12 protein according to the study of Klatt, et al. [ ].

Techniques: Structural Proteomics, Construct, Variant Assay

Journal: BMC Medical Genomics

Article Title: Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy

doi: 10.1186/s12920-023-01780-9

Figure Lengend Snippet: Confidence metrics for the forecasted structure of (A) normal MED12 structure and (B) Val417Ile variant. The Ramachandran plot illustrates the energetically permissible regions for backbone dihedral angles ψ and ϕ of amino acid residues in the MED12 structure (the normal and the Val417Ile variant). The favored, and allowed regions are depicted in green and blue, respectively. (C) The image indicates the possible functions of the native MED12 domains, predicted with the aid of the AlphaFold2 and VAST web servers

Article Snippet: Since it was impossible to model a huge MED12 protein with AlphaFold2 ( https://colab.research.google.com/github/sokrypton/ColabFold/blob/main/AlphaFold2.ipynb ) methods [ ], the InterPro ( https://www.ebi.ac.uk/interpro/ ) web server [ ] was first employed to identify and select the desired domains of the MED12 protein according to the study of Klatt, et al. [ ].

Techniques: Variant Assay

Journal: BMC Medical Genomics

Article Title: Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy

doi: 10.1186/s12920-023-01780-9

Figure Lengend Snippet: The image demonstrates the molecular docking analysis of the MED12 protein (the normal and variant amino acids) with the CDK8 protein (PDB: 4F6U) by using PyMOL v.2.5.2. (A) The image illustrates the protein-protein interactions between the normal MED12 protein and the CDK8 protein (CDK8: purple; normal MED12: green). (B) The protein-protein interactions between the MED12 variant and the CDK8 protein (CDK8: purple; variant MED12: yellow) are shown herein

Article Snippet: Since it was impossible to model a huge MED12 protein with AlphaFold2 ( https://colab.research.google.com/github/sokrypton/ColabFold/blob/main/AlphaFold2.ipynb ) methods [ ], the InterPro ( https://www.ebi.ac.uk/interpro/ ) web server [ ] was first employed to identify and select the desired domains of the MED12 protein according to the study of Klatt, et al. [ ].

Techniques: Variant Assay, Protein-Protein interactions

Journal: BMC Medical Genomics

Article Title: Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy

doi: 10.1186/s12920-023-01780-9

Figure Lengend Snippet: A schematic interaction of the best docking results of the normal (A) and variant MED12 (B) with CDK8 presented by LigPlus + v.2.2.4 is shown herein. Hydrogen bonding is demonstrated in green

Article Snippet: Since it was impossible to model a huge MED12 protein with AlphaFold2 ( https://colab.research.google.com/github/sokrypton/ColabFold/blob/main/AlphaFold2.ipynb ) methods [ ], the InterPro ( https://www.ebi.ac.uk/interpro/ ) web server [ ] was first employed to identify and select the desired domains of the MED12 protein according to the study of Klatt, et al. [ ].

Techniques: Variant Assay

Journal: Proteomics

Article Title: Discriminating physiological from non-physiological interfaces in structures of protein complexes: a community-wide study

doi: 10.1002/pmic.202200323

Figure Lengend Snippet: Classification performance of AlphaFold2 models predicted for the physiological and non-physiological homo dimers of the benchmark dataset. This is evaluated on the subset of 1480 targets for which results were produced with all AlphaFold2 versions. Column 1 lists the version of AlphaFold used for the predictions, and the score used to quantify the similarity between the AlphaFold2 predicted model, and the homodimer structures of the corresponding benchmark entry (see Main text for detail). Column 2 lists the Area Under the Curve (AUC) of the ROCs computed using the listed scores. Columns 3 and 4 list the mean and median values for the computed scores considering only the physiological dimers. Those for the non-physiological dimers are not reported, as AlphaFold2 tends to predict alternative association modes for a significant fraction of these dimers, as expected.

Article Snippet: G.T., L.P., and T.S. acknowledge the contributions of Gabriel Studer in setting up the AlphaFold pipeline for our analysis, sciCORE at the University of Basel for providing computational resources and system administration support, and funding from the SIB Swiss Institute of Bioinformatics and the Biozentrum PhD Fellowships.

Techniques: Produced