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G W Litman

Publications and source records attributed to G W Litman.

135 records · Page 8Linked to original sources
PubMed1970

Conformational significance of the intrachain disulfide linkages in immunoglobulins.

Biophysical studies of intact immunoglobulins, enzymatically derived immunoglobulin subunits, and chemically derived immunoglobulin chains are reported. All the forms studied lacked optical activity associated with the alpha-helix conformation. A dichroism band centered near 217 nm, which has been assigned to the beta-sheet conformation, was present in all subunits that contained at least two covalently linked intrachain disulfide loop regions. This dichroism band could not be detected in Component II, the C-terminal 120 amino acids of the heavy chain. The reduction and alkylation of the intrachain disulfide linkages caused a large conformational change associated with short range interactions. The cleavage of the intrachain disulfide also produced a large change in the environment of two aromatic amino acids, tyrosine and tryptophan. These observations indicate some unique conformational relationships for immunoglobins which may be related to the functional demands placed on this class of macromolecule.

Alkylation↗
PubMedDate not supplied

Major reorganization of immunoglobulin VH segmental elements during vertebrate evolution.

In mammals, the immunoglobulin heavy-chain variable region (VH) locus is organized in a linear fashion; individual VH, diversity (DH), joining (JH) and constant (CH) region segments are linked in separate regions. During somatic development, coding segments flanked by characteristic short recombination signal sequences, separated by intervening sequence regions that may exceed 2,000 kilobases (kb), are recombined. Combinatorial joining of different segments as well as imprecision in this process contribute to the diversity of the primary antibody response; subsequent mutation further alters functionally rearranged genes. This basic somatic reorganization mechanism is shared by six major families of genes encoding antigen receptors. Previously, we have shown that multiple germline genes and mammalian-like recombination signal sequences are associated with the VH gene family of Heterodontus francisci (horned shark), a primitive elasmobranch. Studies presented here demonstrate that segmental reorganization involving mammalian-like DH and JH segments occurs in the lymphoid tissues of this species. In marked contrast to the mammalian system, we find multiple instances of close linkage (approximately 10 kb) between individual VH, DH, JH, and CH segments. This unique organization may limit combinatorial joining and be a factor in the restricted antibody response of this lower vertebrate.

Amino Acid Sequence↗