The Design of Repeat Proteins: Stability Conflicts with Functionality,

Alekhya Thirunahari*

Department of Biotechnology, Osmania University, Hyderabad, Telangana, India

*Corresponding Author:
Alekhya Thirunahari
Department of Biotechnology
Osmania University
Hyderabad, Telangana, India
Tel: 551832291000
E-mail: [email protected]

Received Date: June 05, 2021; Accepted Date: June 10, 2021; Published Date: June 15, 2021

Citation: Thirunahari A (2021) The Design of Repeat Proteins: Stability Conflicts with Functionality. Biochem Mol Biol Vol. 7, No.6: 28.

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A variable number of copies of a given structural piece are tandemly repeated along a longitudinal axis to form repeat proteins. They primarily serve as protein-protein interactors with binding interfaces that are unique to each interacting pair and are not conserved across members of the same family. These proteins have been widely employed as scaffolds for protein design, which is mainly focused on increasing the repeat array stability. Although overall stability is critical for producing molecules with improved solubility and expression, naturally occurring repeat proteins have unstable features that affect their binding capabilities. The current state of the art for repetitive protein designs is discussed, as well as the possibility of enabling energetic conflicts to introduce greater functionality into arrays.

Scientists have fantasised of being able to create and manufacture new proteins for specific purposes as more sequences, structures, and activities concerning proteins have been found. When globular proteins fold, residues that are widely apart in sequence are brought closer together in space. This makes determining how sequence perturbations propagate to the structure, the general dynamics, and finally their impact on protein function more difficult. Repeat proteins may be able to help with this issue. A variable number of core structural elements are repeated in tandem along a longitudinal axis to form repeat proteins.

They can take on many shapes depending on the geometrical and symmetry relationships between recurring modules. On these molecules, residue-residue interactions are mainly restricted to each repetition or to the interfaces between neighbouring repetitions, and local perturbations are not transferred to distant parts of the structure in principle.

Repeat proteins are widely observed mediating protein-protein interactions in their natural environment, and their specificity rivals that of antibodies. As a result, it's not surprising that various organisations have successfully used them as scaffolds for the construction of protein inter actors.

As discussed in, designed repeat proteins have higher thermal stabilities than natural repeat proteins. While high stability is desirable for producing well-expressed and foldable polypeptides, most natural proteins are only moderately stable. It has been hypothesised that protein functionality may be favoured by marginal stability since it is linked to higher flexibility, and that this may boost "functionality." Proteins' exploration of conformational states is increasingly acknowledged as critical to their function, since it allows them to move between the various conformers that make up their native state and therefore perform their function. Is maximising of stability the ideal coordinate for protein design if proteins are inherently moderately stable? Protein folding is explained by the energy landscapes theory, which states that proteins reduce internal conflicts as they fold towards forms that are more akin to their native state.

The upshot of native contacts' cooperativity is a universal decrease of internal energy defined as "the concept of minimal frustration." Natural sequences are polypeptide chains in which the preponderance of natural connections are preferred over any other alternative interaction. Although reduced, the idea of minimal frustration does not rule out the possibility of some energy conflicts persisting in their natural conditions. Furthermore, it has been demonstrated that 10% of all interactions in a monomeric, foldable protein structure are in conflict with their immediate environment on average. These "extremely frustrated" interactions, which have been preserved throughout the evolutionary history of proteins, are critical for a variety of natural protein functions.

Current methods for designing repeat proteins rely on the implicit or explicit optimization of stability, despite the fact that nature is said to care about proteins' capacity to operate in their environment. The importance of energy conflicts in naturally existing repeat proteins is discussed here, as well as why they should be considered when using them as scaffolds for protein design.

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