Publications by authors named "B Wicky"
Pseudosymmetric hetero-oligomers with three or more unique subunits with overall structural (but not sequence) symmetry play key roles in biology, and systematic approaches for generating such proteins de novo would provide new routes to controlling cell signaling and designing complex protein materials. However, the de novo design of protein hetero-oligomers with three or more distinct chains with nearly identical structures is a challenging unsolved problem because it requires the accurate design of multiple protein-protein interfaces simultaneously. Here, we describe a divide-and-conquer approach that breaks the multiple-interface design challenge into a set of more tractable symmetric single-interface redesign tasks, followed by structural recombination of the validated homo-oligomers into pseudosymmetric hetero-oligomers.
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- MERS-CoV is a serious virus with a 36% death rate in humans, and there's currently no vaccine or treatment approved for use in humans or camels.
- Researchers developed special miniproteins that effectively bind to and neutralize various forms of the MERS-CoV spike protein, which is crucial for the virus's ability to infect cells.
- Testing in mice showed that administering one of these miniproteins intranasally can protect against MERS-CoV infection, suggesting potential for further clinical development as a new preventive measure against this virus.
Natural proteins are highly optimized for function but are often difficult to produce at a scale suitable for biotechnological applications due to poor expression in heterologous systems, limited solubility, and sensitivity to temperature. Thus, a general method that improves the physical properties of native proteins while maintaining function could have wide utility for protein-based technologies. Here, we show that the deep neural network ProteinMPNN, together with evolutionary and structural information, provides a route to increasing protein expression, stability, and function.
View Article and Find Full Text PDFHallucination of closed repeat proteins containing central pockets.
Nat Struct Mol Biol
November 2023
Article Synopsis
- Pseudocyclic proteins, like TIM barrels and β barrels, have a repeating subunit structure that creates a central cavity for binding ligands or facilitating enzymatic activity.
- A new deep-learning approach was developed to explore a variety of closed repeat proteins based on specific parameters like repeat number and length.
- Experimental data from diverse pseudocyclic designs shows alignment with the design models, and the crystal structures confirm the accuracy of the designs, suggesting potential for developing small-molecule binders and enzymes.
Targeted intracellular delivery via receptor-mediated endocytosis requires the delivered cargo to escape the endosome to prevent lysosomal degradation. This can in principle be achieved by membrane lysis tightly restricted to endosomal membranes upon internalization to avoid general membrane insertion and lysis. Here, we describe the design of small monomeric proteins with buried histidine containing pH-responsive hydrogen bond networks and membrane permeating amphipathic helices.
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