Comparing the Hinge-Type Mobility of Natural and Designed Intermolecular Bi-disulfide Domains
A pair of intermolecular disulfide bonds connecting two protein domains restricts their relative mobility in a systematic way. The bi-disulfide hinge cannot rotate like a single intermolecular disulfide bond yet is less restrained than three or more intermolecular disulfides which restrict the relat...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2020.00025/full |
| _version_ | 1818944801140113408 |
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| author | Philip Horx Armin Geyer |
| author_facet | Philip Horx Armin Geyer |
| author_sort | Philip Horx |
| collection | DOAJ |
| description | A pair of intermolecular disulfide bonds connecting two protein domains restricts their relative mobility in a systematic way. The bi-disulfide hinge cannot rotate like a single intermolecular disulfide bond yet is less restrained than three or more intermolecular disulfides which restrict the relative motion to a minimum. The intermediate mobility of bi-disulfide linked domains is characterized by their dominating opening and closing modes comparable to the mechanics of a door hinge on the macroscopic scale. Here we compare the central hinge region of Immunoglobulin G1 (IgG1) which is highly conserved among different species, with a recently designed hinge-type motif CHWECRGCRLVC from our lab, that was successfully used for the dimerization of the IgG1/κ-ab CL4 monocolonal antibody (mab). The minimal length of these synthetic hinges comprises only 12 amino acids, rendering them ideal models for computational studies. Well-tempered metadynamics was performed to adequately describe the available conformational space defined by the different hinges. In spite of the differences in amino acid composition and ring sizes, there are characteristic similarities of designed and natural hinges like the dependent mobility of the individual strands of each hinge domain. |
| first_indexed | 2024-12-20T07:48:59Z |
| format | Article |
| id | doaj.art-e341832847d24a1c9b320dea2e8b3c43 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-20T07:48:59Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-e341832847d24a1c9b320dea2e8b3c432022-12-21T19:47:53ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462020-01-01810.3389/fchem.2020.00025510260Comparing the Hinge-Type Mobility of Natural and Designed Intermolecular Bi-disulfide DomainsPhilip HorxArmin GeyerA pair of intermolecular disulfide bonds connecting two protein domains restricts their relative mobility in a systematic way. The bi-disulfide hinge cannot rotate like a single intermolecular disulfide bond yet is less restrained than three or more intermolecular disulfides which restrict the relative motion to a minimum. The intermediate mobility of bi-disulfide linked domains is characterized by their dominating opening and closing modes comparable to the mechanics of a door hinge on the macroscopic scale. Here we compare the central hinge region of Immunoglobulin G1 (IgG1) which is highly conserved among different species, with a recently designed hinge-type motif CHWECRGCRLVC from our lab, that was successfully used for the dimerization of the IgG1/κ-ab CL4 monocolonal antibody (mab). The minimal length of these synthetic hinges comprises only 12 amino acids, rendering them ideal models for computational studies. Well-tempered metadynamics was performed to adequately describe the available conformational space defined by the different hinges. In spite of the differences in amino acid composition and ring sizes, there are characteristic similarities of designed and natural hinges like the dependent mobility of the individual strands of each hinge domain.https://www.frontiersin.org/article/10.3389/fchem.2020.00025/fullhinge-peptidebi-disulfidemodelingantibodiesmetadynamic |
| spellingShingle | Philip Horx Armin Geyer Comparing the Hinge-Type Mobility of Natural and Designed Intermolecular Bi-disulfide Domains Frontiers in Chemistry hinge-peptide bi-disulfide modeling antibodies metadynamic |
| title | Comparing the Hinge-Type Mobility of Natural and Designed Intermolecular Bi-disulfide Domains |
| title_full | Comparing the Hinge-Type Mobility of Natural and Designed Intermolecular Bi-disulfide Domains |
| title_fullStr | Comparing the Hinge-Type Mobility of Natural and Designed Intermolecular Bi-disulfide Domains |
| title_full_unstemmed | Comparing the Hinge-Type Mobility of Natural and Designed Intermolecular Bi-disulfide Domains |
| title_short | Comparing the Hinge-Type Mobility of Natural and Designed Intermolecular Bi-disulfide Domains |
| title_sort | comparing the hinge type mobility of natural and designed intermolecular bi disulfide domains |
| topic | hinge-peptide bi-disulfide modeling antibodies metadynamic |
| url | https://www.frontiersin.org/article/10.3389/fchem.2020.00025/full |
| work_keys_str_mv | AT philiphorx comparingthehingetypemobilityofnaturalanddesignedintermolecularbidisulfidedomains AT armingeyer comparingthehingetypemobilityofnaturalanddesignedintermolecularbidisulfidedomains |