Imitating the humoral immune response.
The immune system makes use of two distinct mechanisms to mount an efficient response against almost every foreign macromolecular substance. First, antibodies with their robust immunoglobulin domain architecture provide a rigid scaffold to support six hypervariable loops, capable of forming highly diverse binding sites. Second, an efficient genetic mechanism has evolved to create sequence diversity at the somatic level in a step-wise process, whereby random recombination of an inherited set of gene segments is followed by hypermutation events. Insight into the corresponding molecular mechanisms is developing rapidly and enables adaptation of the emerging principles to the creation of artificial binding proteins in vitro, using the techniques of combinatorial biotechnology. Thus, novel types of receptor molecules have been constructed from alternative scaffolds, including alpha-helical bundle and beta-barrel proteins. These may provide superior tools for the recognition, targeting or separation of a wide range of biomolecular structures or substances in biological research, technology, and even medicine.
Skerra
Arne
A
Lehrstuhl für Biologische Chemie, Technische Universität Munich, Wissenschaftszentrum Weihenstephan, An der Saatzucht 5, D-85350 Freising, Germany. skerra@wzw.tum.de
D000906:Antibodies / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000916:Antibody Diversity; D000917:Antibody Formation / Q000276:immunology*; D001666:Binding Sites, Antibody; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic
D000906:Antibodies; D007136:Immunoglobulins; D011971:Receptors, Immunologic