A hinge region mutation in C1-inhibitor (Ala436-->Thr) results in nonsubstrate-like behavior and in polymerization of the molecule
| Autoři: | Aulak, K. S., Eldering, E., Hack, C. E., Lubbers, Y. P., Harrison, R. A., Mast, A., Cicardi, M., Davis, A. E. |
|---|---|
| Přispěvatelé: | Other departments |
| Zdroj: | Journal of biological chemistry, 268(24), 18088-18094. American Society for Biochemistry and Molecular Biology Inc. |
| Rok vydání: | 1993 |
| Popis: | C1-inhibitor(Mo), a dysfunctional C1-inhibitor molecule produced in two kindred with type II hereditary angioedema, has a mutation at the P10 position (Ala436 to Thr). Like most serpins with hinge region mutations (P14, P12, P10), C1-inhibitor(Mo) loses its inhibitory activity. However, unlike the other hinge region mutations, this mutant is not converted to a substrate. As shown by nondenaturing gel electrophoresis, gel filtration, sucrose density gradient ultracentrifugation, and electron microscopy, C1-inhibitor(Mo) exists in both monomeric and multimeric forms. Polymerization probably results from reactive center loop insertion into the A sheet of an adjacent molecule. Native C1-inhibitor(Mo) was shown to have a thermal stability profile intermediate to those of intact and of cleaved normal C1-inhibitor. Native C1-inhibitor(Mo) did not bind to monoclonal antibody KII, which binds only to reactive center-cleaved normal C1-inhibitor. It did, however, react with monoclonal antibody KOK12, which recognizes complexed or cleaved C1-inhibitor but not intact normal C1-inhibitor. Native C1-inhibitor(Mo), therefore, exists in a conformation similar to the complexed form of normal C1-inhibitor |
| Jazyk: | English |
| ISSN: | 0021-9258 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=narcis______::b409f0b92169a4e34b37c6bbea3dcc7c https://pure.amc.nl/en/publications/a-hinge-region-mutation-in-c1inhibitor-ala436thr-results-in-nonsubstratelike-behavior-and-in-polymerization-of-the-molecule(2f19e31c-4470-4452-b32a-ae121d6dc397).html |
| Rights: | RESTRICTED |
| Přírůstkové číslo: | edsair.narcis........b409f0b92169a4e34b37c6bbea3dcc7c |
| Autor: | Aulak, K. S., Eldering, E., Hack, C. E., Lubbers, Y. P., Harrison, R. A., Mast, A., Cicardi, M., Davis, A. E. |
| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 1993 |
| Zdroj: | Journal of biological chemistry, 268(24), 18088-18094. American Society for Biochemistry and Molecular Biology Inc. |
| ISSN: | 0021-9258 |
| Popis: | C1-inhibitor(Mo), a dysfunctional C1-inhibitor molecule produced in two kindred with type II hereditary angioedema, has a mutation at the P10 position (Ala436 to Thr). Like most serpins with hinge region mutations (P14, P12, P10), C1-inhibitor(Mo) loses its inhibitory activity. However, unlike the other hinge region mutations, this mutant is not converted to a substrate. As shown by nondenaturing gel electrophoresis, gel filtration, sucrose density gradient ultracentrifugation, and electron microscopy, C1-inhibitor(Mo) exists in both monomeric and multimeric forms. Polymerization probably results from reactive center loop insertion into the A sheet of an adjacent molecule. Native C1-inhibitor(Mo) was shown to have a thermal stability profile intermediate to those of intact and of cleaved normal C1-inhibitor. Native C1-inhibitor(Mo) did not bind to monoclonal antibody KII, which binds only to reactive center-cleaved normal C1-inhibitor. It did, however, react with monoclonal antibody KOK12, which recognizes complexed or cleaved C1-inhibitor but not intact normal C1-inhibitor. Native C1-inhibitor(Mo), therefore, exists in a conformation similar to the complexed form of normal C1-inhibitor |
| Databáze: | OpenAIRE |
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