Functional and structural segregation of overlapping helices in HIV-1
Overlapping coding regions balance selective forces between multiple genes. One possible division of nucleotide sequence is that the predominant selective force on a particular nucleotide can be attributed to just one gene. While this arrangement has been observed in regions in which one gene is str...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/72482 |
| _version_ | 1826866815007981568 |
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| author | Maliheh Safari Bhargavi Jayaraman Henni Zommer Shumin Yang Cynthia Smith Jason D Fernandes Alan D Frankel |
| author_facet | Maliheh Safari Bhargavi Jayaraman Henni Zommer Shumin Yang Cynthia Smith Jason D Fernandes Alan D Frankel |
| author_sort | Maliheh Safari |
| collection | DOAJ |
| description | Overlapping coding regions balance selective forces between multiple genes. One possible division of nucleotide sequence is that the predominant selective force on a particular nucleotide can be attributed to just one gene. While this arrangement has been observed in regions in which one gene is structured and the other is disordered, we sought to explore how overlapping genes balance constraints when both protein products are structured over the same sequence. We use a combination of sequence analysis, functional assays, and selection experiments to examine an overlapped region in HIV-1 that encodes helical regions in both Env and Rev. We find that functional segregation occurs even in this overlap, with each protein spacing its functional residues in a manner that allows a mutable non-binding face of one helix to encode important functional residues on a charged face in the other helix. Additionally, our experiments reveal novel and critical functional residues in Env and have implications for the therapeutic targeting of HIV-1. |
| first_indexed | 2024-04-11T10:50:12Z |
| format | Article |
| id | doaj.art-c04a18a42a1f41d393f4480b04eab8d0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2025-02-16T22:07:30Z |
| publishDate | 2022-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c04a18a42a1f41d393f4480b04eab8d02025-01-15T11:51:17ZengeLife Sciences Publications LtdeLife2050-084X2022-05-011110.7554/eLife.72482Functional and structural segregation of overlapping helices in HIV-1Maliheh Safari0https://orcid.org/0000-0002-9511-6481Bhargavi Jayaraman1https://orcid.org/0000-0002-5071-6117Henni Zommer2Shumin Yang3Cynthia Smith4Jason D Fernandes5https://orcid.org/0000-0002-8625-1796Alan D Frankel6https://orcid.org/0000-0002-2525-9508Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; School of Medicine, Tsinghua University, Beijing, ChinaDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United StatesOverlapping coding regions balance selective forces between multiple genes. One possible division of nucleotide sequence is that the predominant selective force on a particular nucleotide can be attributed to just one gene. While this arrangement has been observed in regions in which one gene is structured and the other is disordered, we sought to explore how overlapping genes balance constraints when both protein products are structured over the same sequence. We use a combination of sequence analysis, functional assays, and selection experiments to examine an overlapped region in HIV-1 that encodes helical regions in both Env and Rev. We find that functional segregation occurs even in this overlap, with each protein spacing its functional residues in a manner that allows a mutable non-binding face of one helix to encode important functional residues on a charged face in the other helix. Additionally, our experiments reveal novel and critical functional residues in Env and have implications for the therapeutic targeting of HIV-1.https://elifesciences.org/articles/72482HIV-1overlapping genesoverprintingEnvRevlentivirus |
| spellingShingle | Maliheh Safari Bhargavi Jayaraman Henni Zommer Shumin Yang Cynthia Smith Jason D Fernandes Alan D Frankel Functional and structural segregation of overlapping helices in HIV-1 eLife HIV-1 overlapping genes overprinting Env Rev lentivirus |
| title | Functional and structural segregation of overlapping helices in HIV-1 |
| title_full | Functional and structural segregation of overlapping helices in HIV-1 |
| title_fullStr | Functional and structural segregation of overlapping helices in HIV-1 |
| title_full_unstemmed | Functional and structural segregation of overlapping helices in HIV-1 |
| title_short | Functional and structural segregation of overlapping helices in HIV-1 |
| title_sort | functional and structural segregation of overlapping helices in hiv 1 |
| topic | HIV-1 overlapping genes overprinting Env Rev lentivirus |
| url | https://elifesciences.org/articles/72482 |
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