Histidinerich

Histidinerich describes proteins or regions within proteins that contain a high proportion of histidine residues. The term is used in sequence descriptions and functional annotations to indicate a low-complexity region enriched in histidine. Histidine-rich regions are characterized by clusters of histidine (H) residues, often interspersed with other amino acids, and may form flexible, poorly structured segments.

Functions and significance: The imidazole side chain of histidine has a pKa near physiological pH, enabling it to participate in proton transfer and metal binding. Histidine-rich motifs commonly act as metal-binding sites, coordinating zinc, nickel, copper, or iron ions, and are important in metalloenzymes, metal storage proteins, and metal transport proteins. They are also exploited in biotechnology: polyhistidine tags (often six consecutive histidines) enable affinity purification of recombinant proteins by immobilized metal affinity chromatography (IMAC). In some organisms, histidine-rich proteins, such as histidine-rich glycoprotein in humans or histidine-rich proteins in Plasmodium falciparum (HRP2), contribute to physiological processes or serve as diagnostic markers.

Occurrence and examples: Histidine-rich regions occur across diverse species and protein families, from secreted glycoproteins to intracellular enzymes. Notable examples include histidine-rich glycoprotein (HRG) in humans and histidine-rich protein 2 (HRP2) produced by Plasmodium falciparum, the latter of interest for malaria diagnostics due to its abundance of histidine repeats.

Considerations: Histidine-rich regions can influence protein solubility, stability, and interactions, and may present challenges for structural characterization. They are often targeted in purification strategies using His-tags but may require optimization to avoid aggregation or proteolysis.