ColabFold: making protein folding accessible to all

Mirdita, Milot; Schütze, Konstantin; Moriwaki, Yoshitaka; Heo, Lim; Овчинников, С. Г.; Steinegger, Martin

doi:10.1038/s41592-022-01488-1

Cited by 4,800 publications

(4,428 citation statements)

References 33 publications

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“…Structures for wildtype and mutant fukutin were calculated with ColabFold [ 23 ]. Structures with the highest per-residue confidence metric (predicted Local Distance Difference Test, pLDDT with 100 = most confident) were chosen (wildtype: pLDDT = 92.19, p.Ser299Arg: pLDDT = 92.17, and p.Asn442Ser: pLDDT = 91.69) and aligned pairwise ( Figure 5 ).…”

Section: Resultsmentioning

confidence: 99%

“…Application of three-dimensional molecular modelling with calculated fukutin structures [ 23 ] revealed a change in polar contacts for the p.Ser299Arg mutant ( Figure 5 ). However, since the major structure of the mutants showed a high degree of alignment with the wildtype protein, it still remains unclear which effects the observed change will have on the enzyme activity or localization of fukutin.…”

Section: Discussionmentioning

confidence: 99%

“…Structures for the wildtype and mutant fukutin were calculated using ColabFold [ 23 ] on the default settings. Structures were refined with Amber-Relax.…”

Section: Methodsmentioning

confidence: 99%

“… Molecular modelling of the FKTN variants p.Ser299Arg (left panel) and p.Asn442Ser (right panel), with structures calculated using ColabFold [ 23 ]. The influence of the variants on the molecular structure was analyzed using PyMOL Molecular Graphics System (version 2.5.2, Schrodinger LLC, New York, NY, USA).…”

Section: Figurementioning

confidence: 99%

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Compound Heterozygous FKTN Variants in a Patient with Dilated Cardiomyopathy Led to an Aberrant α-Dystroglycan Pattern

Gärtner

Burr

Klauke

et al. 2022

IJMS

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Fukutin encoded by FKTN is a ribitol 5-phosphate transferase involved in glycosylation of α-dystroglycan. It is known that mutations in FKTN affect the glycosylation of α-dystroglycan, leading to a dystroglycanopathy. Dystroglycanopathies are a group of syndromes with a broad clinical spectrum including dilated cardiomyopathy and muscular dystrophy. In this study, we reported the case of a patient with muscular dystrophy, early onset dilated cardiomyopathy, and elevated creatine kinase levels who was a carrier of the compound heterozygous variants p.Ser299Arg and p.Asn442Ser in FKTN. Our work showed that compound heterozygous mutations in FKTN lead to a loss of fully glycosylated α-dystroglycan and result in cardiomyopathy and end-stage heart failure at a young age.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Structures for the wildtype and mutant fukutin were calculated using ColabFold [ 23 ] on the default settings. Structures were refined with Amber-Relax.…”

Section: Methodsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Compound Heterozygous FKTN Variants in a Patient with Dilated Cardiomyopathy Led to an Aberrant α-Dystroglycan Pattern

Gärtner

Burr

Klauke

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…SMYD AF structures and their expected position errors were downloaded from the AlphaFold Protein Structure Database. AF prediction of SMYD5 structures was performed by using the AlphaFold CoLab notebook (Phenix version) [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Unique SMYD5 Structure Revealed by AlphaFold Correlates with Its Functional Divergence

et al. 2022

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SMYD5 belongs to a special class of protein lysine methyltransferases with an MYND (Myeloid-Nervy-DEAF1) domain inserted into a SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) domain. Despite recent advances in its functional characterization, the lack of the crystal structure has hindered our understanding of the structure-and-function relationships of this most unique member of the SMYD protein family. Here, we demonstrate the reliability of using AlphaFold structures for understanding the structure and function of SMYD5 by comparing the AlphaFold structures to the known crystal structures of SMYD proteins, using an inter-residue distance maps-based metric. We found that the AlphaFold confidence scores are inversely associated with the refined B-factors and can serve as a structural indicator of conformational flexibility. We also found that the N-terminal sequence of SMYD5, predicted to be a mitochondrial targeting signal, contains a novel non-classical nuclear localization signal. This sequence is structurally flexible and does not have a well-defined conformation, which might facilitate its recognition for SMYD5′s cytonuclear transport. The structure of SMYD5 is unique in many aspects. The “crab”-like structure with a large negatively charged cleft provides a potential binding site for basic molecules such as protamines. The less positively charged MYND domain is associated with the undetectable DNA-binding ability. The most surprising feature is an incomplete target lysine access channel that lacks the evolutionarily conserved tri-aromatic arrangement, being associated with the low H3/H4 catalytic activity. This study expands our understanding of the SMYD protein family from a classical two-lobed structure to a structure of its own kind, being as a fundamental determinant of its functional divergence.

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Two phosphoenolpyruvate carboxykinases with differing biochemical properties in Chlamydomonas reinhardtii

et al. 2023

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Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the reversible reaction of decarboxylation and phosphorylation of oxaloacetate (OAA) to generate phosphoenolpyruvate (PEP) and CO2 playing mainly a gluconeogenic role in green algae. We found two PEPCK isoforms in Chlamydomonas reinhardtii and we cloned, purified and characterised both enzymes. ChlrePEPCK1 is more active as decarboxylase than ChlrePEPCK2. ChlrePEPCK1 is hexameric and its activity is affected by citrate, phenylalanine and malate, while ChlrePEPCK2 is monomeric and it is regulated by citrate, phenylalanine and glutamine. We postulate that the two PEPCK isoforms found originate from alternative splicing of the gene or regulated proteolysis of the enzyme. The presence of these two isoforms would be part of a mechanism to finely regulate the biological activity of PEPCKs.

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ColabFold: making protein folding accessible to all

Cited by 4,800 publications

References 33 publications

Compound Heterozygous FKTN Variants in a Patient with Dilated Cardiomyopathy Led to an Aberrant α-Dystroglycan Pattern

Compound Heterozygous FKTN Variants in a Patient with Dilated Cardiomyopathy Led to an Aberrant α-Dystroglycan Pattern

Unique SMYD5 Structure Revealed by AlphaFold Correlates with Its Functional Divergence

Two phosphoenolpyruvate carboxykinases with differing biochemical properties in Chlamydomonas reinhardtii

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