linkerregion

Linker region, sometimes written linkerregion, is a term used in molecular biology to describe a stretch of amino acids that connects two or more functional regions within a protein or protein complex. Linker regions can be native to the protein or introduced through genetic engineering. They vary in length from a few residues to over a hundred and may be unstructured and highly flexible or adopt defined secondary structures depending on sequence and context.

Characteristics: often enriched in small, flexible residues such as glycine and serine; may be intrinsically disordered; their sequence determines flexibility, rotational freedom, and the relative orientation of connected domains; some linkers are designed to be rigid, for example by forming alpha helices with proline or alanine residues.

Functions: allow domain movements, prevent steric clash, facilitate substrate transfer, influence overall stability and folding; impact catalytic efficiency; in antibodies, the hinge region acts as a natural flexible linker between Fab and Fc regions; in metabolic enzymes, linkers can modulate allostery.

Engineering and design: in fusion proteins or modular enzymes, linker design is critical; factors include length, flexibility, avoidance of protease sites, immunogenicity, and compatibility with expression host; common choices include short flexible linkers like GGGGS repeats, or rigid linkers like EAAAK sequences.

Research and resources: studied by structural biology and biophysics; linked to intrinsically disordered regions; important in protein engineering; practitioners assess using NMR, SAXS, FRET, and related techniques to infer flexibility and domain orientation.