The human γG1 myeloma protein Eu was isolated in pure form, and the protein was characterized to provide data for more detailed structural analyses. The molecular weight of the native molecule was 154,000 ± 8,000, as measured by sedimentation equilibrium. The component light (molecular weight 22,500) and heavy (molecular weight 51,600) chains were isolated in high yield by gel filtration after reduction and alkylation under mild conditions. Amino terminal analyses and the amino acid compositions of the native molecule and its chains indicated that there were two light and two heavy chains per molecule of Eu. Limited digestion of Eu with trypsin yielded Fab(t) and Fc(t) fragments, which were immunologically identical to Fab and Fc fragments produced by papain digestion. Amino acid analysis showed 32 residues of half-cystine per mole of Eu, with 5 in each light chain and 11 in each heavy chain. The half-cystinyl residues in the light chain are located at positions 23(I), 88(II), 134(III), 194(IV), and 214(V). The half-cystinyl residues in the heavy chain are located at positions 22(I), 96(II), 144(III), 200(IV), 220(V), 226(VI), 229(VII), 261(VIII), 321(IX), 367(X), and 425(XI). There were no free sulfhydryl groups in the protein, indicating that there are 16 disulfide bonds. Reduction of Eu under mild conditions indicated that there were four interchain bonds, and peptides containing these bonds were isolated. A bond between half-cystines L-V and H-V links each light chain to its corresponding heavy chain; this bond is in the Fab(t) region of the molecule. There are two bonds linking the heavy chains between corresponding half-cystines H-VI and H-VII; these bonds are in the Fc(t) region of the molecule. All of the half-cystinyl residues forming the interchain bonds are located between residues 220 and 229 of the heavy chain in what may be a \"hinge\" region of the molecule. The remaining twelve half-cystines form intrachain bonds. The two intrachain bonds in each light chain are formed by half-cystines L-I and L-II, and by L-III and L-IV. The four intrachain bonds in the heavy chain are made up of half-cystines H-I and H-II, H-III and H-IV, H-VIII and H-IX, and H-X and H-XI. These bonds have a linear and periodic arrangement. Each bond forms a loop about 60 residues long. This structure provides evidence for theories on the evolution of immunoglobulins by gene duplication. This pattern also suggests that the immunoglobulin molecule may be folded in compact domains and that each domain contains one disulfide loop. Each variable region of the molecule contains one disulfide loop which may serve to fix the position of the antigen-binding site in the tertiary structure of the molecule.
","abstract_html":"<p>The human γG1 myeloma protein Eu was isolated in pure form, and the protein was characterized to provide data for more detailed structural analyses. The molecular weight of the native molecule was 154,000 ± 8,000, as measured by sedimentation equilibrium. The component light (molecular weight 22,500) and heavy (molecular weight 51,600) chains were isolated in high yield by gel filtration after reduction and alkylation under mild conditions. Amino terminal analyses and the amino acid compositions of the native molecule and its chains indicated that there were two light and two heavy chains per molecule of Eu. Limited digestion of Eu with trypsin yielded Fab(t) and Fc(t) fragments, which were immunologically identical to Fab and Fc fragments produced by papain digestion. Amino acid analysis showed 32 residues of half-cystine per mole of Eu, with 5 in each light chain and 11 in each heavy chain. The half-cystinyl residues in the light chain are located at positions 23(I), 88(II), 134(III), 194(IV), and 214(V). The half-cystinyl residues in the heavy chain are located at positions 22(I), 96(II), 144(III), 200(IV), 220(V), 226(VI), 229(VII), 261(VIII), 321(IX), 367(X), and 425(XI). There were no free sulfhydryl groups in the protein, indicating that there are 16 disulfide bonds. Reduction of Eu under mild conditions indicated that there were four interchain bonds, and peptides containing these bonds were isolated. A bond between half-cystines L-V and H-V links each light chain to its corresponding heavy chain; this bond is in the Fab(t) region of the molecule. There are two bonds linking the heavy chains between corresponding half-cystines H-VI and H-VII; these bonds are in the Fc(t) region of the molecule. All of the half-cystinyl residues forming the interchain bonds are located between residues 220 and 229 of the heavy chain in what may be a "hinge" region of the molecule. The remaining twelve half-cystines form intrachain bonds. The two intrachain bonds in each light chain are formed by half-cystines L-I and L-II, and by L-III and L-IV. The four intrachain bonds in the heavy chain are made up of half-cystines H-I and H-II, H-III and H-IV, H-VIII and H-IX, and H-X and H-XI. These bonds have a linear and periodic arrangement. Each bond forms a loop about 60 residues long. This structure provides evidence for theories on the evolution of immunoglobulins by gene duplication. This pattern also suggests that the immunoglobulin molecule may be folded in compact domains and that each domain contains one disulfide loop. Each variable region of the molecule contains one disulfide loop which may serve to fix the position of the antigen-binding site in the tertiary structure of the molecule.</p>","abstract_has_math":false,"creators":["Gall, William Einar"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Gerald Edelman"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1969,"date_issued":"1969-01-01T08:00:00Z","date_published":"1969-01-01T08:00:00Z","updated_at":"2026-07-24T04:11:11Z","subjects":["immunoglobulin","disulfide bonds","heavy chain","light chain","myeloma protein","Fab and Fc fragments","Life Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/594","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Gerald Edelman"]},{"key":"dc:creator","label":"Author","values":["Gall, William Einar"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["immunoglobulin","disulfide bonds","heavy chain","light chain","myeloma protein","Fab and Fc fragments","Life Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/594"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The human γG1 myeloma protein Eu was isolated in pure form, and the protein was characterized to provide data for more detailed structural analyses. The molecular weight of the native molecule was 154,000 ± 8,000, as measured by sedimentation equilibrium. The component light (molecular weight 22,500) and heavy (molecular weight 51,600) chains were isolated in high yield by gel filtration after reduction and alkylation under mild conditions. Amino terminal analyses and the amino acid compositions of the native molecule and its chains indicated that there were two light and two heavy chains per molecule of Eu. Limited digestion of Eu with trypsin yielded Fab(t) and Fc(t) fragments, which were immunologically identical to Fab and Fc fragments produced by papain digestion. Amino acid analysis showed 32 residues of half-cystine per mole of Eu, with 5 in each light chain and 11 in each heavy chain. The half-cystinyl residues in the light chain are located at positions 23(I), 88(II), 134(III), 194(IV), and 214(V). The half-cystinyl residues in the heavy chain are located at positions 22(I), 96(II), 144(III), 200(IV), 220(V), 226(VI), 229(VII), 261(VIII), 321(IX), 367(X), and 425(XI). There were no free sulfhydryl groups in the protein, indicating that there are 16 disulfide bonds. Reduction of Eu under mild conditions indicated that there were four interchain bonds, and peptides containing these bonds were isolated. A bond between half-cystines L-V and H-V links each light chain to its corresponding heavy chain; this bond is in the Fab(t) region of the molecule. There are two bonds linking the heavy chains between corresponding half-cystines H-VI and H-VII; these bonds are in the Fc(t) region of the molecule. All of the half-cystinyl residues forming the interchain bonds are located between residues 220 and 229 of the heavy chain in what may be a \"hinge\" region of the molecule. The remaining twelve half-cystines form intrachain bonds. The two intrachain bonds in each light chain are formed by half-cystines L-I and L-II, and by L-III and L-IV. The four intrachain bonds in the heavy chain are made up of half-cystines H-I and H-II, H-III and H-IV, H-VIII and H-IX, and H-X and H-XI. These bonds have a linear and periodic arrangement. Each bond forms a loop about 60 residues long. This structure provides evidence for theories on the evolution of immunoglobulins by gene duplication. This pattern also suggests that the immunoglobulin molecule may be folded in compact domains and that each domain contains one disulfide loop. Each variable region of the molecule contains one disulfide loop which may serve to fix the position of the antigen-binding site in the tertiary structure of the molecule.
"]},{"key":"dc:title","label":"Title","values":["The Arrangement of the Disulfide Bonds in a γG Immunoglobulin Molecule"]}]}],"canonical_facts":{"dc:contributor":["Gerald Edelman"],"dc:creator":["Gall, William Einar"],"dc:description.abstract":["The human γG1 myeloma protein Eu was isolated in pure form, and the protein was characterized to provide data for more detailed structural analyses. The molecular weight of the native molecule was 154,000 ± 8,000, as measured by sedimentation equilibrium. The component light (molecular weight 22,500) and heavy (molecular weight 51,600) chains were isolated in high yield by gel filtration after reduction and alkylation under mild conditions. Amino terminal analyses and the amino acid compositions of the native molecule and its chains indicated that there were two light and two heavy chains per molecule of Eu. Limited digestion of Eu with trypsin yielded Fab(t) and Fc(t) fragments, which were immunologically identical to Fab and Fc fragments produced by papain digestion. Amino acid analysis showed 32 residues of half-cystine per mole of Eu, with 5 in each light chain and 11 in each heavy chain. The half-cystinyl residues in the light chain are located at positions 23(I), 88(II), 134(III), 194(IV), and 214(V). The half-cystinyl residues in the heavy chain are located at positions 22(I), 96(II), 144(III), 200(IV), 220(V), 226(VI), 229(VII), 261(VIII), 321(IX), 367(X), and 425(XI). There were no free sulfhydryl groups in the protein, indicating that there are 16 disulfide bonds. Reduction of Eu under mild conditions indicated that there were four interchain bonds, and peptides containing these bonds were isolated. A bond between half-cystines L-V and H-V links each light chain to its corresponding heavy chain; this bond is in the Fab(t) region of the molecule. There are two bonds linking the heavy chains between corresponding half-cystines H-VI and H-VII; these bonds are in the Fc(t) region of the molecule. All of the half-cystinyl residues forming the interchain bonds are located between residues 220 and 229 of the heavy chain in what may be a \"hinge\" region of the molecule. The remaining twelve half-cystines form intrachain bonds. The two intrachain bonds in each light chain are formed by half-cystines L-I and L-II, and by L-III and L-IV. The four intrachain bonds in the heavy chain are made up of half-cystines H-I and H-II, H-III and H-IV, H-VIII and H-IX, and H-X and H-XI. These bonds have a linear and periodic arrangement. Each bond forms a loop about 60 residues long. This structure provides evidence for theories on the evolution of immunoglobulins by gene duplication. This pattern also suggests that the immunoglobulin molecule may be folded in compact domains and that each domain contains one disulfide loop. Each variable region of the molecule contains one disulfide loop which may serve to fix the position of the antigen-binding site in the tertiary structure of the molecule.
"],"dc:identifier":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/594"],"dc:subject":["immunoglobulin","disulfide bonds","heavy chain","light chain","myeloma protein","Fab and Fc fragments","Life Sciences"],"dc:title":["The Arrangement of the Disulfide Bonds in a γG Immunoglobulin Molecule"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:11:11Z"}