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Báo cáo khoa học: Alternative binding proteins: Anticalins – harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities

Antibodies are the paradigm for binding proteins, with their hypervariable loop region supported by a structurally rigid framework, thus providing the vast repertoire of antigen-binding sites in the immune system. Lipoca-lins are another family of proteins that exhibit a binding site with high structural plasticity, which is composed of four peptide loops mounted on a stable b-barrel scaffold. | ỊFEBS Journal MINIREVIEW Alternative binding proteins Anticalins - harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities Arne Skerra Lehrstuhl fur Biologische Chemie Technische Universitat Munchen Freising-Weihenstephan Germany Keywords bacterialexpression b-barrel CTLA-4 digitalis fluorescein ligand binding lipocalin molecular recognition protein engineering VEGF Correspondence A. Skerra Lehrstuhlfur Biologische Chemie Technische Universitat Munchen An der Saatzucht 5 85350 Freising-Weihenstephan Germany Fax 49 8161 714352 Tel 49 8161 714351 E-mail skerra@wzw.tum.de Received 16 November 2007 revised 9 March 2008 accepted 22 March 2008 doi 10.1111 j.1742-4658.2008.06439.x Antibodies are the paradigm for binding proteins with their hypervariable loop region supported by a structurally rigid framework thus providing the vast repertoire of antigen-binding sites in the immune system. Lipoca-lins are another family of proteins that exhibit a binding site with high structural plasticity which is composed of four peptide loops mounted on a stable b-barrel scaffold. Using site-directed random mutagenesis and selection via phage display against prescribed molecular targets it is possible to generate artificial lipocalins with novel ligand specificities so-called anticalins. Anticalins have been successfully selected both against small hapten-like compounds and against large protein antigens and they usually possess high target affinity and specificity. Their structural analysis has yielded interesting insights into the phenomenon of molecular recognition. Compared with antibodies they are much smaller have a simpler molecular architecture comprising just one polypeptide chain and they do not require post-translational modification. In addition anticalins exhibit robust biophysical properties and can easily be produced in microbial expression systems. As their structure-function relationships are well understood rational .