Related Experiment Video
Updated: Mar 5, 2026
09:34
Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly
Published on: February 6, 2020
8.0K
Computational design of self-assembling cyclic protein homo-oligomers
Jorge A Fallas1,2, George Ueda1,2, William Sheffler1,2
1Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Nature Chemistry
|March 25, 2017
Summary
Scientists developed a new computational method to design cyclic protein homo-oligomers. This approach successfully created stable, custom protein structures with cyclic symmetry, advancing protein engineering capabilities.
Area of Science:
- Structural Biology
- Protein Engineering
- Computational Biology
Background:
- Self-assembling cyclic protein homo-oligomers are crucial in biological processes.
- Designing custom homo-oligomeric structures offers novel avenues for biological research.
Purpose of the Study:
- To develop a general computational approach for designing de novo cyclic protein homo-oligomers.
- To enable the creation of protein complexes with specific cyclic symmetries.
Main Methods:
- Introduced a novel residue-pair-transform method to evaluate protein-protein interface designability.
- Systematically enumerated cyclically docked monomer arrangements.
- Applied sequence design to newly formed interfaces on idealized repeat proteins.
Main Results:
- 21 out of 96 experimentally characterized designs formed stable, monodisperse homo-oligomers in solution.
- 15 designs showed solution small-angle X-ray scattering (SAXS) data consistent with designed cyclic models (dimers, trimers, tetramers, pentamers).
- X-ray crystal structures of five designs closely matched their computational models.
Conclusions:
- The developed computational method is effective for designing cyclic protein homo-oligomers.
- Experimental validation confirms the successful creation of stable, custom cyclic protein assemblies.
- This work provides a powerful tool for protein design and the study of biological functions.
Related Concept Videos
02:41Protein Complex Assembly
17.0K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
17.0K
01:22Protein Folding
129.4K
Overview
129.4K
01:25Protein Folding
12.0K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
12.0K
01:18Assembly of Cytoskeletal Filaments
28.1K
Cytoskeletal filaments are polymeric forms of smaller protein subunits. However, individual cytoskeletal filaments may easily disassemble or associate with other similar filaments to form rigid structures. Microfilaments, made of actin monomers, rely on actin-binding proteins to form bundles and create networks of individual actin filaments. Microtubules rely on microtubule-associated proteins (MAPs) to form sturdy cylindrical structures. However, the proteins involved in forming complex...
28.1K
01:57Protein Complexes with Interchangeable Parts
3.0K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
3.0K
03:00Molecular Chaperones and Protein Folding
20.6K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
20.6K