Background: Reelin is a large glycoprotein critical in brain development and functions as a form of multimer. Results: Disulfide-bonded homodimer through Cys 2101 is the functional unit of biologically active reelin protein. Conclusion:An intact higher order architecture of reelin multimer is essential for exerting its full biological activity. Significance: Ultrastructural and biochemical characterization of gigantic reelin protein is crucial for mechanistic understanding of reelin signaling.

Biologically important human proteins often require mammalian cell expression for structural studies, presenting technical and economical problems in the production/purification processes. We introduce a novel affinity peptide tagging system that uses a low affinity anti-peptide monoclonal antibody. Concatenation of the short recognition sequence enabled the successful engineering of an 18-residue affinity tag with ideal solution binding kinetics, providing a low-cost purification means when combined with nondenaturing elution by water-miscible organic solvents. Three-dimensional information provides a firm structural basis for the antibody-peptide interaction, opening opportunities for further improvements/modifications.