Transactivation domain of Adenovirus Early Region 1A (E1A): Investigating folding dynamics and aggregation
Transactivation domain of Adenovirus Early region 1A (E1A) oncoprotein is an intrinsically disordered molecular hub protein. It is involved in binding to different domains of human cell transcriptional co-activators such as retinoblastoma (pRb), CREB-binding protein (CBP), and its paralogue p300. Th...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
|
| Series: | Current Research in Structural Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665928X22000010 |
| _version_ | 1798006929130258432 |
|---|---|
| author | Nitin Sharma Kundlik Gadhave Prateek Kumar Rajanish Giri |
| author_facet | Nitin Sharma Kundlik Gadhave Prateek Kumar Rajanish Giri |
| author_sort | Nitin Sharma |
| collection | DOAJ |
| description | Transactivation domain of Adenovirus Early region 1A (E1A) oncoprotein is an intrinsically disordered molecular hub protein. It is involved in binding to different domains of human cell transcriptional co-activators such as retinoblastoma (pRb), CREB-binding protein (CBP), and its paralogue p300. The conserved region 1 (TAD) of E1A is known to undergo structural transitions and folds upon interaction with transcriptional adaptor zinc finger 2 (TAZ2). Previous reports on Taz2-E1A studies have suggested the formation of helical conformations of E1A-TAD. However, the folding behavior of the TAD region in isolation has not been studied in detail. Here, we have elucidated the folding behavior of E1A peptide at varied temperatures and solution conditions. Further, we have studied the effects of macromolecular crowding on E1A-TAD peptide. Additionally, we have also predicted the molecular recognition features of E1A using MoRF predictors. The predicted MoRFs are consistent with its structural transitions observed during TAZ2 interactions for transcriptional regulation in literature. Also, as a general rule of MoRFs, E1A undergoes helical transitions in alcohol and osmolyte solution. Finally, we studied the aggregation behavior of E1A, where we observed that the E1A could form amyloid-like aggregates that are cytotoxic to mammalian cells. |
| first_indexed | 2024-04-11T13:03:21Z |
| format | Article |
| id | doaj.art-fbabc190ca9c41e3aaa5068f92d9a77f |
| institution | Directory Open Access Journal |
| issn | 2665-928X |
| language | English |
| last_indexed | 2024-04-11T13:03:21Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Structural Biology |
| spelling | doaj.art-fbabc190ca9c41e3aaa5068f92d9a77f2022-12-22T04:22:53ZengElsevierCurrent Research in Structural Biology2665-928X2022-01-0142940Transactivation domain of Adenovirus Early Region 1A (E1A): Investigating folding dynamics and aggregationNitin Sharma0Kundlik Gadhave1Prateek Kumar2Rajanish Giri3School of Basic Sciences, Indian Institute of Technology Mandi, Kamand, Himachal Pradesh, 175005, IndiaSchool of Basic Sciences, Indian Institute of Technology Mandi, Kamand, Himachal Pradesh, 175005, IndiaSchool of Basic Sciences, Indian Institute of Technology Mandi, Kamand, Himachal Pradesh, 175005, IndiaSchool of Basic Sciences, Indian Institute of Technology Mandi, Kamand, Himachal Pradesh, 175005, India; BioX Center, Indian Institute of Technology Mandi, Kamand, Himachal Pradesh, 175005, India; Corresponding author. School of Basic Sciences, Indian Institute of Technology Mandi, Himachal Pradesh, 175005, India.Transactivation domain of Adenovirus Early region 1A (E1A) oncoprotein is an intrinsically disordered molecular hub protein. It is involved in binding to different domains of human cell transcriptional co-activators such as retinoblastoma (pRb), CREB-binding protein (CBP), and its paralogue p300. The conserved region 1 (TAD) of E1A is known to undergo structural transitions and folds upon interaction with transcriptional adaptor zinc finger 2 (TAZ2). Previous reports on Taz2-E1A studies have suggested the formation of helical conformations of E1A-TAD. However, the folding behavior of the TAD region in isolation has not been studied in detail. Here, we have elucidated the folding behavior of E1A peptide at varied temperatures and solution conditions. Further, we have studied the effects of macromolecular crowding on E1A-TAD peptide. Additionally, we have also predicted the molecular recognition features of E1A using MoRF predictors. The predicted MoRFs are consistent with its structural transitions observed during TAZ2 interactions for transcriptional regulation in literature. Also, as a general rule of MoRFs, E1A undergoes helical transitions in alcohol and osmolyte solution. Finally, we studied the aggregation behavior of E1A, where we observed that the E1A could form amyloid-like aggregates that are cytotoxic to mammalian cells.http://www.sciencedirect.com/science/article/pii/S2665928X22000010Intrinsically disordered proteinsMolecular recognition elementsE1AProtein foldingProtein aggregation |
| spellingShingle | Nitin Sharma Kundlik Gadhave Prateek Kumar Rajanish Giri Transactivation domain of Adenovirus Early Region 1A (E1A): Investigating folding dynamics and aggregation Current Research in Structural Biology Intrinsically disordered proteins Molecular recognition elements E1A Protein folding Protein aggregation |
| title | Transactivation domain of Adenovirus Early Region 1A (E1A): Investigating folding dynamics and aggregation |
| title_full | Transactivation domain of Adenovirus Early Region 1A (E1A): Investigating folding dynamics and aggregation |
| title_fullStr | Transactivation domain of Adenovirus Early Region 1A (E1A): Investigating folding dynamics and aggregation |
| title_full_unstemmed | Transactivation domain of Adenovirus Early Region 1A (E1A): Investigating folding dynamics and aggregation |
| title_short | Transactivation domain of Adenovirus Early Region 1A (E1A): Investigating folding dynamics and aggregation |
| title_sort | transactivation domain of adenovirus early region 1a e1a investigating folding dynamics and aggregation |
| topic | Intrinsically disordered proteins Molecular recognition elements E1A Protein folding Protein aggregation |
| url | http://www.sciencedirect.com/science/article/pii/S2665928X22000010 |
| work_keys_str_mv | AT nitinsharma transactivationdomainofadenovirusearlyregion1ae1ainvestigatingfoldingdynamicsandaggregation AT kundlikgadhave transactivationdomainofadenovirusearlyregion1ae1ainvestigatingfoldingdynamicsandaggregation AT prateekkumar transactivationdomainofadenovirusearlyregion1ae1ainvestigatingfoldingdynamicsandaggregation AT rajanishgiri transactivationdomainofadenovirusearlyregion1ae1ainvestigatingfoldingdynamicsandaggregation |