Modulation of the vault protein-protein interaction for tuning of molecular release
Vaults are naturally occurring ovoid nanoparticles constructed from a protein shell that is composed of multiple copies of major vault protein (MVP). The vault-interacting domain of vault poly(ADP-ribose)-polymerase (INT) has been used as a shuttle to pack biomolecular cargo in the vault lumen. Howe...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/88105 http://hdl.handle.net/10220/45629 |
| _version_ | 1826118103244734464 |
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| author | Yu, Kang Yau, Yin Hoe Sinha, Ameya Tan, Tabitha Kickhoefer, Valerie A. Rome, Leonard H. Lee, Hwankyu Shochat, Susana G. Lim, Sierin |
| author2 | School of Chemical and Biomedical Engineering |
| author_facet | School of Chemical and Biomedical Engineering Yu, Kang Yau, Yin Hoe Sinha, Ameya Tan, Tabitha Kickhoefer, Valerie A. Rome, Leonard H. Lee, Hwankyu Shochat, Susana G. Lim, Sierin |
| author_sort | Yu, Kang |
| collection | NTU |
| description | Vaults are naturally occurring ovoid nanoparticles constructed from a protein shell that is composed of multiple copies of major vault protein (MVP). The vault-interacting domain of vault poly(ADP-ribose)-polymerase (INT) has been used as a shuttle to pack biomolecular cargo in the vault lumen. However, the interaction between INT and MVP is poorly understood. It is hypothesized that the release rate of biomolecular cargo from the vault lumen is related to the interaction between MVP and INT. To tune the release of molecular cargos from the vault nanoparticles, we determined the interactions between the isolated INT-interacting MVP domains (iMVP) and wild-type INT and compared them to two structurally modified INT: 15-amino acid deletion at the C terminus (INTΔC15) and histidine substituted at the interaction surface (INT/DSA/3 H) to impart a pH-sensitive response. The apparent affinity constants determined using surface plasmon resonance (SPR) biosensor technology are 262 ± 4 nM for iMVP/INT, 1800 ± 160 nM for iMVP/INTΔC15 at pH 7.4. The INT/DSA/3 H exhibits stronger affinity to iMVP (K Dapp = 24 nM) and dissociates at a slower rate than wild-type INT at pH 6.0. |
| first_indexed | 2024-10-01T04:38:15Z |
| format | Journal Article |
| id | ntu-10356/88105 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:38:15Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/881052023-12-29T06:48:04Z Modulation of the vault protein-protein interaction for tuning of molecular release Yu, Kang Yau, Yin Hoe Sinha, Ameya Tan, Tabitha Kickhoefer, Valerie A. Rome, Leonard H. Lee, Hwankyu Shochat, Susana G. Lim, Sierin School of Chemical and Biomedical Engineering School of Materials Science & Engineering School of Biological Sciences NTU-Northwestern Institute for Nanomedicine Molecular Release Vault DRNTU::Engineering::Bioengineering Vaults are naturally occurring ovoid nanoparticles constructed from a protein shell that is composed of multiple copies of major vault protein (MVP). The vault-interacting domain of vault poly(ADP-ribose)-polymerase (INT) has been used as a shuttle to pack biomolecular cargo in the vault lumen. However, the interaction between INT and MVP is poorly understood. It is hypothesized that the release rate of biomolecular cargo from the vault lumen is related to the interaction between MVP and INT. To tune the release of molecular cargos from the vault nanoparticles, we determined the interactions between the isolated INT-interacting MVP domains (iMVP) and wild-type INT and compared them to two structurally modified INT: 15-amino acid deletion at the C terminus (INTΔC15) and histidine substituted at the interaction surface (INT/DSA/3 H) to impart a pH-sensitive response. The apparent affinity constants determined using surface plasmon resonance (SPR) biosensor technology are 262 ± 4 nM for iMVP/INT, 1800 ± 160 nM for iMVP/INTΔC15 at pH 7.4. The INT/DSA/3 H exhibits stronger affinity to iMVP (K Dapp = 24 nM) and dissociates at a slower rate than wild-type INT at pH 6.0. Published version 2018-08-20T06:40:28Z 2019-12-06T16:56:06Z 2018-08-20T06:40:28Z 2019-12-06T16:56:06Z 2017 Journal Article Yu, K., Yau, Y. H., Sinha, A., Tan, T., Kickhoefer, V. A., Rome, L. H., . . . Lim, S. (2017). Modulation of the vault protein-protein interaction for tuning of molecular release. Scientific Reports, 7, 14816-. doi:10.1038/s41598-017-12870-x 2045-2322 https://hdl.handle.net/10356/88105 http://hdl.handle.net/10220/45629 10.1038/s41598-017-12870-x en Scientific Reports © 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 10 p. application/pdf |
| spellingShingle | Molecular Release Vault DRNTU::Engineering::Bioengineering Yu, Kang Yau, Yin Hoe Sinha, Ameya Tan, Tabitha Kickhoefer, Valerie A. Rome, Leonard H. Lee, Hwankyu Shochat, Susana G. Lim, Sierin Modulation of the vault protein-protein interaction for tuning of molecular release |
| title | Modulation of the vault protein-protein interaction for tuning of molecular release |
| title_full | Modulation of the vault protein-protein interaction for tuning of molecular release |
| title_fullStr | Modulation of the vault protein-protein interaction for tuning of molecular release |
| title_full_unstemmed | Modulation of the vault protein-protein interaction for tuning of molecular release |
| title_short | Modulation of the vault protein-protein interaction for tuning of molecular release |
| title_sort | modulation of the vault protein protein interaction for tuning of molecular release |
| topic | Molecular Release Vault DRNTU::Engineering::Bioengineering |
| url | https://hdl.handle.net/10356/88105 http://hdl.handle.net/10220/45629 |
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