Crystal structures of human antibodies: a detailed and unfinished tapestry of immunoglobulin gene products.
Sequencing of all human immunoglobulin (Ig) germline gene segments has recently been completed. However, our first glimpses of the recombined products of this combinatorial gene system were in the 1970s, in landmark publications, reporting the crystal structures of two human myeloma proteins, the Mcg lambda light chain dimer and the New IgG1(lambda) Fab. Although numerous crystal structures of murine and human antibodies have now been determined, only a relatively small proportion of the human germline genes have had their corresponding protein three-dimensional structures resolved. Therefore, further structural investigations are required before the inherent diversity of the antibody repertoire can be fully appreciated. We discuss the detailed structural information available for human antibodies with regard to their immune functions. Also discussed, is how the structural information is finding application in the 'humanization' of murine antibodies as part of their development as 'biopharmaceuticals' for the treatment of human disease.
Ramsland
Paul A
PA
Structural Biology Laboratory, The Austin Research Institute, Studley Road, Heidelberg, Victoria 3084, Australia. p.ramsland@ari.unimelb.edu.au
Farrugia
William
W
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use; D000916:Antibody Diversity; D001666:Binding Sites, Antibody; D018360:Crystallography, X-Ray; D005803:Genes, Immunoglobulin; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D015202:Protein Engineering; D017434:Protein Structure, Tertiary
D000911:Antibodies, Monoclonal; D007127:Immunoglobulin Constant Regions; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins