Db. Huang et al., VARIABLE DOMAIN-STRUCTURE OF KAPPA-IV HUMAN LIGHT-CHAIN LEN - HIGH HOMOLOGY TO THE MURINE LIGHT-CHAIN MCPC603, Molecular immunology, 34(18), 1997, pp. 1291-1301
Antibody light chains of the kappa subgroup are the predominant light
chain component in human immune responses and are used almost exclusiv
ely in the antibody repertoire of mice. Human kappa light chains compr
ise four subgroups. To date, all crystallographic studies of human kap
pa light chains were carried out on proteins of the kappa I subgroup.
The light chain produced by multiple myeloma patient Len, was of the k
appa IV subgroup, it differed by only one residue from the germ-line g
ene encoded protein. The variable domain fragment of the light chain w
as crystallized from ammonium sulfate in space group C222(1). The crys
tal structure was determined by molecular replacement and refined at 1
.95 Angstrom resolution to an R-factor of 0.15. Protein Len has six ad
ditional residues in its CDR1 segment compared to the kappa I proteins
previously characterized. The kappa IV variable domain, Len, differs
in only 23 of 113 residues from murine kappa light chain McPC603. The
RMS deviation upon superimposing their alpha-carbons was 0.69 Angstrom
. The CDRI segment of the human and murine variable domains have the s
ame length and conformation although their amino acid sequences differ
in 5 out of 17 residues. Structural features were identified that cou
ld account for the significantly higher stability of the human kappa I
V protein relative to its murine counterpart. This human kappa IV ligh
t chain structure is the closest human homolog to a murine light chain
and can be expected to facilitate detailed structural comparisons nec
essary for effective humanization of murine antibodies. (C) 1998 Publi
shed by Elsevier Science Ltd. All rights reserved.