The Three - Dimensional Structure of the Fab ' Fragment of a Human Myeloma lmmunoglobulin at 2 . 0 - A Resolution

The structural analysis of the Fab' fragment of human myeloma immunoglobulin IgGl(X) New has been extended to a nominal resolution of 2.0 A. Each of the structural subunits corresponding to the variable and to the constant homology regions of the light and heavy chains contains two irregular f:l-sheets which are roughly parallel to each other and surround a tightly packed interior of hydrophobic side chains. About 50-60% of the amino-acid residues are included in {:j-pleated sheets. Sequence alignments between the homology regions of Fab' New obtained by comparison of their three-dimensional structures are given. Some of the sequence variations observed in light and heavy chains and the role of the regions of hypervariable sequence in defining the size and shape of the active site of different immunoglobulin molecules are discussed on the basis of the three-dimensional model of Fab' New. In a previous paper (2) we described the three-Oimensional structure of the Fab' fragment of human myeloma immunoglobulin lgG New based on the interpretation of an electron density map at 2.8-A resolution. The molecule was found to consist of four globular subunits which correspond to the variable (VL, VH) and constant (CL and Cal) homology regions of the light (L) and heavy (H) polypeptide chains, arranged in tetrahedral configuration. The homology subunits*, which closely resemble each other, share a basic pattern of polypeptide chain folding. This basic pattern (immunoglobulin fold) and an additional loop of polypeptide chain describe the more complex folding of the variable subunits. The additional loop in the VL subunit of lgG New is shortened by a deletion of seven amino acids which is unique to this L chain. The regions of hypervariable sequence in the L and H chains were found to occur in close spatial proximity, at one end of the molecule. Two reports dealing with the three-dimensional structure of human immunoglobulin L chains have been published (3, 4). In this paper we extend-the structural analysis of Fab' New to a nominal resolution of 2.0 A and continue the description and discussion of its three-dimensional structure.