 Peptide linker

A peptide linker is a peptide segment connecting protein components within one continuous polypeptide chain. It joins their backbones while allowing relative positioning that depends on the segment's sequence and conformation. The connected regions can be distinct protein domains or components brought together in a fusion protein.

For an original residue-accounting example, components of 180 and 240 amino acid residues joined by a six-residue peptide linker produce a chain of 426 residues. Replacing that connector with an eighteen-residue peptide linker produces 438 residues. The twelve-residue difference specifies a sequence-length change; it does not uniquely determine the end-to-end distance of a polymer chain, binding affinity or catalytic rate.

A structural experiment illustrates why the distinction matters. Researchers tethered adrenodoxin to the cholesterol side-chain cleavage enzyme through different peptide linkers. The resulting crystallizable fusion proteins captured a similar interface, yet their catalytic activities differed from the nonfused comparison, and electron transfer depended on linker length even when substrate affinity was preserved.^[ref]

Linker choice is therefore part of the experiment. Structural capture, substrate recognition and catalytic performance are separate readouts. Success at one of them does not establish that the connector reproduces every property of the freely associating components.