Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide
Plasmodium falciparum FK506-binding protein 35 (PfFKBP35) that binds to FK506 contains a conserved tetratricopeptide repeat (TPR) domain. Several known TPR domains such as Hop, PPP5, CHIP, and FKBP52 are structurally conserved and are able to interact with molecular chaperones such as Hsp70/Hsp90. H...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2012
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| Online Access: | https://hdl.handle.net/10356/95073 http://hdl.handle.net/10220/8710 |
| _version_ | 1826121378442510336 |
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| author | Alag, Reema Bharatham, Nagakumar Dong, Aiping Hills, Tanya Harikishore, Amaravadhi Widjaja, Anissa Anindya Shochat, Susana Geifman Hui, Raymond Yoon, Ho Sup |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Alag, Reema Bharatham, Nagakumar Dong, Aiping Hills, Tanya Harikishore, Amaravadhi Widjaja, Anissa Anindya Shochat, Susana Geifman Hui, Raymond Yoon, Ho Sup |
| author_sort | Alag, Reema |
| collection | NTU |
| description | Plasmodium falciparum FK506-binding protein 35 (PfFKBP35) that binds to FK506 contains a conserved tetratricopeptide repeat (TPR) domain. Several known TPR domains such as Hop, PPP5, CHIP, and FKBP52 are structurally conserved and are able to interact with molecular chaperones such as Hsp70/Hsp90. Here, we present the crystal structure of PfFKBP35-TPR and demonstrate its interaction with Hsp90 C-terminal pentapeptide (MEEVD) by surface plasmon resonance and nuclear magnetic resonance spectroscopy-based binding studies. Our sequence and structural analyses reveal that PfFKBP35 is similar to Hop and PPP5 in possessing all the conserved residues which are important for carboxylate clamping with Hsp90. Mutational studies were carried out on positively charged clamp residues that are crucial for binding to carboxylate groups of aspartate, showing that all the mutated residues are important for Hsp90 binding. Molecular docking and electrostatic calculations demonstrated that the MEEVD peptide of Hsp90 can form aspartate clamp unlike FKBP52. Our results provide insightful information and structural basis about the molecular interaction between PfFKBP35-TPR and Hsp90. |
| first_indexed | 2024-10-01T05:31:22Z |
| format | Journal Article |
| id | ntu-10356/95073 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:31:22Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | ntu-10356/950732022-02-16T16:30:31Z Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide Alag, Reema Bharatham, Nagakumar Dong, Aiping Hills, Tanya Harikishore, Amaravadhi Widjaja, Anissa Anindya Shochat, Susana Geifman Hui, Raymond Yoon, Ho Sup School of Biological Sciences DRNTU::Science::Chemistry::Analytical chemistry::Proteins Plasmodium falciparum FK506-binding protein 35 (PfFKBP35) that binds to FK506 contains a conserved tetratricopeptide repeat (TPR) domain. Several known TPR domains such as Hop, PPP5, CHIP, and FKBP52 are structurally conserved and are able to interact with molecular chaperones such as Hsp70/Hsp90. Here, we present the crystal structure of PfFKBP35-TPR and demonstrate its interaction with Hsp90 C-terminal pentapeptide (MEEVD) by surface plasmon resonance and nuclear magnetic resonance spectroscopy-based binding studies. Our sequence and structural analyses reveal that PfFKBP35 is similar to Hop and PPP5 in possessing all the conserved residues which are important for carboxylate clamping with Hsp90. Mutational studies were carried out on positively charged clamp residues that are crucial for binding to carboxylate groups of aspartate, showing that all the mutated residues are important for Hsp90 binding. Molecular docking and electrostatic calculations demonstrated that the MEEVD peptide of Hsp90 can form aspartate clamp unlike FKBP52. Our results provide insightful information and structural basis about the molecular interaction between PfFKBP35-TPR and Hsp90. 2012-10-05T04:14:21Z 2019-12-06T19:07:40Z 2012-10-05T04:14:21Z 2019-12-06T19:07:40Z 2009 2009 Journal Article Alag, R., Bharatham, N., Dong, A., Hills, T., Harikishore, A., Widjaja, A. A., et al. (2009). Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide. Protein Science, 18(10), 2115-2124. https://hdl.handle.net/10356/95073 http://hdl.handle.net/10220/8710 10.1002/pro.226 19691130 en Protein science © 2009 The Protein Society |
| spellingShingle | DRNTU::Science::Chemistry::Analytical chemistry::Proteins Alag, Reema Bharatham, Nagakumar Dong, Aiping Hills, Tanya Harikishore, Amaravadhi Widjaja, Anissa Anindya Shochat, Susana Geifman Hui, Raymond Yoon, Ho Sup Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide |
| title | Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide |
| title_full | Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide |
| title_fullStr | Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide |
| title_full_unstemmed | Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide |
| title_short | Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide |
| title_sort | crystallographic structure of the tetratricopeptide repeat domain of plasmodium falciparum fkbp35 and its molecular interaction with hsp90 c terminal pentapeptide |
| topic | DRNTU::Science::Chemistry::Analytical chemistry::Proteins |
| url | https://hdl.handle.net/10356/95073 http://hdl.handle.net/10220/8710 |
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