The three-dimensional structure of human serum albumin has been determined crystallographically to a resolution of 2.8 A. It comprises three homologous domains that assemble to form a heart-shaped molecule. Each domain is a product of two subdomains that possess common structural motifs. The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar chemistry. The structure explains numerous physical phenomena and should provide insight into future pharmacokinetic and genetically engineered therapeutic applications of serum albumin.

The three-dimensional structure of a human monoclonal antibody (Fab), which binds speciflcally to a major epitope of the transmembrane protein gp4l of the human Immunodeficiency virus type 1, has been determined by crystallographic methods to a resolution of 2.7 A. It has been previously determined that this antibody recognizes the epitope SGKLICTTAVPWNAS, belongs to the subclass IgG1 (me), and exhibits antibody-dependent cellular cytotoxicity. The quaternary structure of the Fab is in an extended conformation with an elbow bend ange between the constant and variable domains of 175°. Struc y, four of the hypervariable loops can be classified according to previously recognized canonical structures. The third hypervariable loops of the heavy (H3) and light chain (L3) are structurally distinct. Hypervariable loop H3, residues 102H-109H, is unusually extended from the surface. The complementarity-determining region forms a hydrophobic binding pocket that is created primarily from hypervariable loops L3, 13, and H2.To date there have been several antibody structures complexed with antigens (1-7) and numerous Fab structures determined by crystallographic methods. Details of the intermolecular contacts in these complexes vary considerably and may include a number of salt bridges, hydrogen bonds, and hydrophobic interactions (8). Despite the small number of completed structures compared with the virtually unlimited number of possible paratopes, evidence for discrete conformational patterns among five of the six antibody hypervariable regions (L1, L2, L3, H1, H2) is emerging (9, 10). Recognition of these canonical structures, and the development of new accurate ab-initio (11) and database modeling algorithms (12)(13)(14), has aided the development of predictive methods that allow antibody combining sites to be more accurately modeled from sequence data alone (15).Currently, the growing body of structural data on immunoglobulins and their complexes with antigens, together with the implementation of site-directed mutagenesis and the creation of smaller Fv proteins by recombinant methods, is providing a more complete understanding of antibody structure and antibody-antigen interaction (16)(17)(18)(19)(20). These advances in knowledge also promise avenues for new therapeutic approaches to various immunologically recognizable illnesses, including the acquired immunodeficiency syndrome (AIDS) (21).This structural work is part of a series that aims to elucidate the detailed nature ofhuman monoclonal antibodies expressed against the AIDS virus together with their respective antigen complexes. Atomic coordinates produced from these studies should (i) provide important information for future recombinant experiments with genetically engineered antibodies and smaller Fv proteins, (ii) guide chemists in the selection of superior antigenic peptides for human immunodeficiency virus (HIV) detection, (iii) yield further insight into the details of antibody-antigen recognition, and (iv) aid in future crystal structure solutions of...

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