Accurate prediction of protein structures and interactions using a three-track neural network

Baek, Minkyung; DiMaio, Frank; Anishchenko, Ivan; Dauparas, Justas; Овчинников, С. Г.; Lee, Gyu Rie; Wang, Jue; Cong, Qian; Kinch, Lisa N.; Schaeffer, R. Dustin; Millán, Claudia; Park, Hahnbeom; Adams, Carson; Glassman, Caleb R.; DeGiovanni, Andy; Pereira, J.H.; Rodrigues, Andria V.; Dijk, Alberdina A. van; Ebrecht, Ana Cristina; Opperman, Diederik J.; Sagmeister, Theo; Buhlheller, Christoph; Pavkov‐Keller, Tea; Rathinaswamy, Manoj Kumar; Dalwadi, Udit; Yip, Calvin K.; Burke, John E.; García, K. Christopher; Grishin, Nick V.; Adams, Paul D.; Read, Randy J.; Baker, David

doi:10.1126/science.abj8754

Cited by 3,607 publications

(3,096 citation statements)

References 76 publications

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“…23a ). Of note, our MymK model shares high similarity with that predicted by AlphaFold2 (AF-A6NI61-F1-model_v1) 39 and RoseTTAFold 40 , two other neural network-based methods.…”

Section: Resultsmentioning

confidence: 62%

Evolution of a chordate-specific mechanism for myoblast fusion

Zhang

Shang

Kim

et al. 2021

Preprint

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The size of an animal is determined by the size of its musculoskeletal system. Myoblast fusion is an innovative mechanism that allows for multinucleated muscle fibers to compound the size and strength of individual mononucleated cells. However, the evolutionary history of the control mechanism underlying this important process is currently unknown. The phylum Chordata hosts closely related groups that span distinct myoblast fusion states: no fusion in cephalochordates, restricted fusion and multinucleation in tunicates, and extensive, obligatory fusion in vertebrates. To elucidate how these differences may have evolved, we studied the evolutionary origins and function of membrane-coalescing agents Myomaker and Myomixer in various groups of chordates. Here we report that Myomaker likely arose through gene duplication in the last common ancestor of tunicates and vertebrates, while Myomixer appears to have evolved de novo in early vertebrates. Functional tests revealed an unexpectedly complex evolutionary history of myoblast fusion in chordates. A pre-vertebrate phase of muscle multinucleation driven by Myomaker was followed by the later emergence of Myomixer that enables the highly efficient fusion system of vertebrates. Thus, our findings reveal the evolutionary origins of chordate-specific fusogens and illustrate how new genes can shape the emergence of novel morphogenetic traits and mechanisms.

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“…23a ). Of note, our MymK model shares high similarity with that predicted by AlphaFold2 (AF-A6NI61-F1-model_v1) 39 and RoseTTAFold 40 , two other neural network-based methods.…”

Section: Resultsmentioning

confidence: 62%

Evolution of a chordate-specific mechanism for myoblast fusion

Zhang

Shang

Kim

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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“…In the most recent 14th Critical Assessment of Structure Prediction (CASP14), AlphaFold2 achieved a median score of 87.0 GDT for the free modeling category, which is a great improvement. RoseTTAFold 8 was developed using a similar end-to-end network architecture and achieved structure prediction accuracy close to that of AlphaFold2. The high accuracy of AlphaFlold2 make it possible to offer meaningful predicted structures to biologists, which is applied to human genome 9 .…”

Section: Protocol To Identify New Foldsmentioning

confidence: 99%

Rational Exploration of Fold Atlas for Human Solute Carrier Proteins

Xie

Chi

Huang

et al. 2021

Preprint

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Solute carrier superfamily (SLC) is the largest group responsible for transmembrane transport of substances in human cells. It includes more than 400 members that can be divided into 65 families according to their physiological function and sequence similarity. Different families of solute transporters can adopt the same or different folds that determines the working mechanism and reflects the evolutionary relationship between SLC members. Analysis of structural data shows that there are 13 different folds in the solute carrier superfamily covering 40 families and 342 members. To further study their working mechanism, we systematically explored the SLC superfamily to find more folds. Our results indicate that there are at least three new folds in the solute transporter superfamily among which the SLC44 family is experimentally verified to have a new fold. Our work has laid a foundation and provided important insights for the systematic and comprehensive study on the structure and function of solute carriers.

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“…Therefore, we used a molecular modeling approach to explore whether AgMESH extracellular domains could interact with chitin. The overall domain architecture of the AgMESH polypeptide was modelled using the RoseTTAFold algorithm (Figure S3) (53). Individual domains within the A. gambiae MESH sequence and tertiary structural folds were predicted for several putative chitin-interacting or stabilizing domains using homology modeling.…”

Section: Mesh Promotes Integrity Of the Peritrophic Matrixmentioning

confidence: 99%

AgMESH, a peritrophic matrix-associated protein embedded inAnopheles gambiaemelanotic capsules modulates malaria parasite infection

Camacho

Dong

Angleró-Rodríguez

et al. 2021

Preprint

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Melanins are structurally complex pigments produced by organisms in all domains of life from bacteria to animals, including humans. In insects, melanins are essential for survival and have key roles in cuticle sclerotization, wound healing and innate immunity. In this study, we used a diverse set of molecular, biochemical, and imaging approaches to characterize mosquito melanin involved in innate immune defense (melanotic capsules ). We observed that melanotic capsules enclosing Plasmodium berghei ookinetes were composed of an acid-resistant and highly hydrophobic material with granular appearance, which are characteristic properties of melanins. Spectroscopical analyses reveal chemical signatures of eumelanins and pheomelanin. Furthermore, using an enrichment approach for the proteomic analysis, we identified a set of 14 of acid-resistant mosquito proteins embedded within the melanin matrix possibly related to an anti- Plasmodium response. Among these, Ag Mesh, a highly conserved protein among insect species that contains domains suggesting a role in immune recognition and function. We targeted Ag Mesh for further study using a RNAi-based gene silencing approach in mosquitos and challenged them with two Plasmodium spp. Surprisingly, Ag Mesh gene silencing in mosquitos was associated with reduced parasite infection, implying an important role in facilitating vector infection by Plasmodium spp. Our results provide a new approach to study aspects of insect melanogenesis that revealed proteins associated with melanotic capsule, one of which was strongly implicated in the pathogenesis of Plasmodium spp. mosquito infection. Given the conservation of Ag Mesh among disease-transmitting insect vector species, future analysis of this protein could provide fertile ground for the identification of strategies that block transmission of disease to humans.

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Accurate prediction of protein structures and interactions using a three-track neural network

Cited by 3,607 publications

References 76 publications

Evolution of a chordate-specific mechanism for myoblast fusion

Evolution of a chordate-specific mechanism for myoblast fusion

Rational Exploration of Fold Atlas for Human Solute Carrier Proteins

AgMESH, a peritrophic matrix-associated protein embedded inAnopheles gambiaemelanotic capsules modulates malaria parasite infection

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