Linkers: A synergistic way for the synthesis of chimeric proteins

In the cell, the protein domains are attached with the short oligopeptide, commonly known as linker peptide. Besides bridging, the linker assists in the domain-domain interaction and protein folding into the peculiar conformations. Linkers allow or control the movement of protein domains in the dynamic cellular environment. The recent advances in the recombinant DNA technology enable the construction of multiple gene constructs in an open reading frame. The express sequences can work in a cascade to cater for myriad functions. This trend has given momentum to incorporating bridge sequences (linker) that essentially separates the independent domains. According to the cellular need, the bridging partner can be spaced at a secure gap or requires attaching or interacting physically. The flexible or rigid linker can help to achieve such conformations in chimeric fusion proteins. The linker can improve solubility, proteolytic resistance and stability of such fusion proteins. Recently, linker aided protein switches and antibody-drug conjugates are gaining the attention of researchers worldwide. Here, we thoroughly reviewed the types of the linker, strategies for linker engineering and the composition of a linker.

Automated summary

In cells, protein domains are linked by short oligopeptides known as linker peptides, which assist in domain-domain interaction and protein folding in specific conformations. Linkers allow for controlled movement of protein domains in the dynamic cell environment, and recent advances in recombinant DNA technology have enabled the construction of multiple gene constructs with open reading frames. Incorporating bridge sequences (linkers) into independent domains is gaining momentum, with the flexibility to space the bridging partner as needed for cellular function.