Different degrees of interspecies homology in immunoglobulin λ chain constant domain correlated with three-dimensional structure

Novotný, Jiří; Franěk, F.

doi:10.1038/258641a0

Cited by 29 publications

(7 citation statements)

References 18 publications

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“…The conserved segments of the VH region have more to do with protein architecture than the nonconserved portion that is mostly located on the surface. Similar observations have been made for other immunoglobulin domains, such as the A C region (41).…”

Section: Discussionsupporting

confidence: 66%

Evolution of immunoglobulin genes: VH families in the amphibian Xenopus.

Hsu

Schwager

Alt

1989

Proc. Natl. Acad. Sci. U.S.A.

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We have isolated multiple independent cDNA clones that represent mRNA sequences of immunoglobulin heavy chains from the spleen of adult Xenopus laevis. These cDNA clones contained constant (C) region sequences that were either C,, or a separate C region sequence believed to be C,, In individual cDNA clones the C region sequences were associated with independent heavy-chain variable region (VH) sequences that were classifiable into five distinct families. Genomic Southern blotting analyses with family-specific probes indicated that the haploid genome contains a minimum of 80 VH gene segments, a number similar to that found in various mammalian species. Multiple JH and putative DH segments were also identified (J, joining; D, diversity). Analyses of 13 independent VHDJH junctions suggest that combinatorial and junctional diversification mechanisms probably arose early in vertebrate evolution. Finally, comparison of Xenopus VH sequences to those from other vertebrates indicated conservation of V region framework residues that are responsible for the tertiary structure of the Fv throughout evolution.The basic four-chain unit of an immunoglobulin molecule is composed of two heavy (H) and two light (L) chains, the N-terminal (variable, V) regions of which interact to form the antigen-binding site. The immunoglobulin H-chain V region gene (VH) is formed by the joining of three gene segments-VH, DH, and JH-while the L-chain V region gene (VL) is assembled from VL and JL segments (D, diversity; J, joining). These rearranged units are assembled upstream from exons that encode the respective H-or L-chain constant (C) regions and are then transcribed to generate the H-or L-chain mRNA. The antigen contact regions of the H-and L-chain V regions are referred to as complementarity-determining regions (CDRs), which were originally defined from variability plots of numerous V region amino acid sequences (1, 2). Each V region has three CDRs, two of which are encoded in the germ-line V segment (CDR1 and CDR2); the other (CDR3) is encoded by the VDJ and VJ junctional regions.Mammals, chickens, and sharks all assemble and express immunoglobulin H-and L-chain genes by the basic processes outlined above but they differ radically in gene organization and mechanisms to generate an extraordinary diversity of specificities in antibody molecules. The mouse and human generate diversity through a combination of germ-line and somatic processes in which large numbers of germ-line gene segments arranged in tandem as multiple V (containing CDR1 and CDR2), multiple D, and multiple J segments are rearranged somatically in different combinations (to create different CDR3s); in addition, diversity is further augmented by somatic processes of junctional diversification and somatic hypermutation (3, 4). The shark also contains 100-200 germ-

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Section: Discussionsupporting

confidence: 66%

Evolution of immunoglobulin genes: VH families in the amphibian Xenopus.

Hsu

Schwager

Alt

1989

Proc. Natl. Acad. Sci. U.S.A.

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“…/? loops of V domains are solvent-accessible, exposed areas at the surface of the molecule where both convexity and relative rigidity are important factors (Novotny et al 1975). Their conformation is influenced by various factors such as the size, the shape, and contact residues.…”

Section: Antigenization: Structural Considerationsmentioning

confidence: 99%

Theoretical and Practical Aspects of Antigenized Antibodies

Zanetti

Rossi

Lanza

et al. 1992

Immunological Reviews

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“…These segments of course correspond to the non-/?-pleated regions in the domains of the crystallographic models and can be involved in bends, helices or other structure. Novotny & Franek (1975) have compared the amino acid sequences of the C A domains of human (New), mouse (104E and 315) and pig, and find that although there is 51 % identity for the whole domain, there is only 6% in b3 and b5 segments and 67% in fx segments. However, comparison of C y domains and of C K domains shows that b5 is not always unusually variable and that other b segments, and segments fx3, fyi and fy3, sometimes also show marked variation.…”

Section: Evidence For a Common Tertiary Structure For C Domainsmentioning

confidence: 99%