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Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

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Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
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Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
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Protein families are groups of homologous proteins; that is, they have similarities in amino acid sequences and three-dimensional structures. Protein families usually occur because of gene duplication, where an additional copy of a gene is inserted into the genome of an organism.   Mutations that change the amino acids but still allow the protein to be properly synthesized, will lead to new protein family members.   If these new proteins contain similar amino acids in key...
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A sweeter future: Using protein language models for exploring sweeter brazzein homologs.

Bryan Nicholas Chua1, Wei Mei Guo2, Han Teng Wong1

  • 1Molecular Engineering Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, #07-06, Proteos, Singapore 138673, Republic of Singapore.

Food Chemistry
|June 18, 2023
PubMed
Summary

Protein language models designed novel brazzein variants with enhanced thermostability and sweetness, offering a healthier sugar alternative. This computational approach yields optimized amino acid sequences for improved protein function and engineering possibilities.

Keywords:
Alternative sweetenersBrazzeinComputational designGenerative AILactococcus lactisThermostable

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Area of Science:

  • Biotechnology
  • Protein Engineering
  • Computational Biology

Background:

  • Growing health concerns regarding sugar consumption necessitate alternative sweeteners.
  • Brazzein is a promising natural sweetener known for its sweetness, thermostability, and safety profile.
  • Conventional protein engineering methods have limitations in optimizing complex traits like thermostability and sweetness.

Purpose of the Study:

  • To utilize protein language models for designing novel brazzein homologs with enhanced thermostability and sweetness.
  • To generate diverse, optimized amino acid sequences for improved structural and functional features of brazzein.
  • To develop an efficient system for expressing, purifying, and analyzing engineered brazzein variants.

Main Methods:

  • Application of protein language models for de novo protein design.
  • Generation and optimization of amino acid sequences for brazzein.
  • Expression and purification of brazzein mutants using Lactococcus lactis (L. lactis).
  • Evaluation of sweetness using taste receptor assays.

Main Results:

  • Successful design of new brazzein homologs with improved thermostability and potential for higher sweetness.
  • Identification of unexpected mutations leading to novel protein engineering avenues.
  • Development of a simplified and efficient protocol for brazzein mutant characterization.
  • Demonstration of a computationally designed, more heat-resistant, and palatable brazzein variant (V23).

Conclusions:

  • Protein language models are powerful tools for engineering enhanced protein functionalities, such as improved thermostability and sweetness in brazzein.
  • Computational design offers a pathway beyond conventional methods for creating superior protein variants.
  • The developed methodology facilitates efficient characterization of engineered proteins, accelerating future research in protein engineering and sweetener development.