A single amino acid of human immunodeficiency virus type 2 capsid protein affects conformation of two external loops and viral sensitivity to TRIM5α
We previously reported that human immunodeficiency virus type 2 (HIV-2) carrying alanine or glutamine but not proline at position 120 of the capsid protein (CA) could grow in the presence of anti-viral factor TRIM5α of cynomolgus monkey (CM). To elucidate details of the interaction between the CA an...
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| creator | Miyamoto, Tadashi Yokoyama, Masaru Kono, Ken Shioda, Tatsuo Sato, Hironori Nakayama, Emi E |
| description | We previously reported that human immunodeficiency virus type 2 (HIV-2) carrying alanine or glutamine but not proline at position 120 of the capsid protein (CA) could grow in the presence of anti-viral factor TRIM5α of cynomolgus monkey (CM). To elucidate details of the interaction between the CA and TRIM5α, we generated mutant HIV-2 viruses, each carrying one of the remaining 17 possible amino acid residues, and examined their sensitivity to CM TRIM5α-mediated restriction. Results showed that hydrophobic residues or those with ring structures were associated with sensitivity, while those with small side chains or amide groups conferred resistance. Molecular dynamics simulation study revealed a structural basis for the differential TRIM5α sensitivities. The mutations at position 120 in the loop between helices 6 and 7 (L6/7) affected conformation of the neighboring loop between helices 4 and 5 (L4/5), and sensitive viruses had a common L4/5 conformation. In addition, the common L4/5 structures of the sensitive viruses were associated with a decreased probability of hydrogen bond formation between the 97th aspartic acid in L4/5 and the 119th arginine in L6/7. When we introduced aspartic acid-to-alanine substitution at position 97 (D97A) of the resistant virus carrying glutamine at position 120 to disrupt hydrogen bond formation, the resultant virus became moderately sensitive. Interestingly, the virus carrying glutamic acid at position 120 showed resistance, while its predicted L4/5 conformation was similar to those of sensitive viruses. The D97A substitution failed to alter the resistance of this particular virus, indicating that the 120th amino acid residue itself is also involved in sensitivity regardless of the L4/5 conformation. These results suggested that a hydrogen bond between the L4/5 and L6/7 modulates the overall structure of the exposed surface of the CA, but the amino acid residue at position 120 is also directly involved in CM TRIM5α recognition. |
| doi_str_mv | 10.1371/journal.pone.0022779 |
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To elucidate details of the interaction between the CA and TRIM5α, we generated mutant HIV-2 viruses, each carrying one of the remaining 17 possible amino acid residues, and examined their sensitivity to CM TRIM5α-mediated restriction. Results showed that hydrophobic residues or those with ring structures were associated with sensitivity, while those with small side chains or amide groups conferred resistance. Molecular dynamics simulation study revealed a structural basis for the differential TRIM5α sensitivities. The mutations at position 120 in the loop between helices 6 and 7 (L6/7) affected conformation of the neighboring loop between helices 4 and 5 (L4/5), and sensitive viruses had a common L4/5 conformation. In addition, the common L4/5 structures of the sensitive viruses were associated with a decreased probability of hydrogen bond formation between the 97th aspartic acid in L4/5 and the 119th arginine in L6/7. When we introduced aspartic acid-to-alanine substitution at position 97 (D97A) of the resistant virus carrying glutamine at position 120 to disrupt hydrogen bond formation, the resultant virus became moderately sensitive. Interestingly, the virus carrying glutamic acid at position 120 showed resistance, while its predicted L4/5 conformation was similar to those of sensitive viruses. The D97A substitution failed to alter the resistance of this particular virus, indicating that the 120th amino acid residue itself is also involved in sensitivity regardless of the L4/5 conformation. These results suggested that a hydrogen bond between the L4/5 and L6/7 modulates the overall structure of the exposed surface of the CA, but the amino acid residue at position 120 is also directly involved in CM TRIM5α recognition.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0022779</identifier><identifier>PMID: 21829511</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Alanine ; Amino Acid Substitution ; Amino acids ; Animals ; Antiviral agents ; Arginine ; Aspartic acid ; Biology ; Blotting, Western ; Bonding ; Capsid protein ; Capsid Proteins - genetics ; Capsid Proteins - metabolism ; Chain dynamics ; Disease resistance ; Dynamic structural analysis ; Gene expression ; Genomics ; Glutamic acid ; Glutamine ; Helices ; HIV ; HIV Infections - genetics ; HIV Infections - immunology ; HIV Infections - virology ; HIV-1 - genetics ; HIV-1 - immunology ; HIV-2 - genetics ; HIV-2 - growth & development ; HIV-2 - immunology ; Human immunodeficiency virus ; Humans ; Hydrogen ; Hydrogen bonds ; Hydrophobicity ; Infections ; Infectious diseases ; Kinases ; Macaca fascicularis ; Models, Molecular ; Molecular dynamics ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Mutation ; Proline ; Protein Conformation ; Protein structure ; Proteins ; Proteins - chemistry ; Proteins - genetics ; Proteins - immunology ; Residues ; Ring structures ; Sensitivity ; Simian Immunodeficiency Virus - genetics ; Simian Immunodeficiency Virus - growth & development ; Simian Immunodeficiency Virus - immunology ; Simulation ; Studies ; Viral infections ; Virus Replication ; Viruses</subject><ispartof>PloS one, 2011, Vol.6 (7), p.e22779</ispartof><rights>2011 Miyamoto et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Miyamoto et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-3568183fe62af933de64a7f5cd4f1bfafcfaed158921d46e63d5ba4d119b3a93</citedby><cites>FETCH-LOGICAL-c525t-3568183fe62af933de64a7f5cd4f1bfafcfaed158921d46e63d5ba4d119b3a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145752/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145752/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,4022,23865,27922,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21829511$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lee, Young-Min</contributor><creatorcontrib>Miyamoto, Tadashi</creatorcontrib><creatorcontrib>Yokoyama, Masaru</creatorcontrib><creatorcontrib>Kono, Ken</creatorcontrib><creatorcontrib>Shioda, Tatsuo</creatorcontrib><creatorcontrib>Sato, Hironori</creatorcontrib><creatorcontrib>Nakayama, Emi E</creatorcontrib><title>A single amino acid of human immunodeficiency virus type 2 capsid protein affects conformation of two external loops and viral sensitivity to TRIM5α</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>We previously reported that human immunodeficiency virus type 2 (HIV-2) carrying alanine or glutamine but not proline at position 120 of the capsid protein (CA) could grow in the presence of anti-viral factor TRIM5α of cynomolgus monkey (CM). To elucidate details of the interaction between the CA and TRIM5α, we generated mutant HIV-2 viruses, each carrying one of the remaining 17 possible amino acid residues, and examined their sensitivity to CM TRIM5α-mediated restriction. Results showed that hydrophobic residues or those with ring structures were associated with sensitivity, while those with small side chains or amide groups conferred resistance. Molecular dynamics simulation study revealed a structural basis for the differential TRIM5α sensitivities. The mutations at position 120 in the loop between helices 6 and 7 (L6/7) affected conformation of the neighboring loop between helices 4 and 5 (L4/5), and sensitive viruses had a common L4/5 conformation. In addition, the common L4/5 structures of the sensitive viruses were associated with a decreased probability of hydrogen bond formation between the 97th aspartic acid in L4/5 and the 119th arginine in L6/7. When we introduced aspartic acid-to-alanine substitution at position 97 (D97A) of the resistant virus carrying glutamine at position 120 to disrupt hydrogen bond formation, the resultant virus became moderately sensitive. Interestingly, the virus carrying glutamic acid at position 120 showed resistance, while its predicted L4/5 conformation was similar to those of sensitive viruses. The D97A substitution failed to alter the resistance of this particular virus, indicating that the 120th amino acid residue itself is also involved in sensitivity regardless of the L4/5 conformation. These results suggested that a hydrogen bond between the L4/5 and L6/7 modulates the overall structure of the exposed surface of the CA, but the amino acid residue at position 120 is also directly involved in CM TRIM5α recognition.</description><subject>Acids</subject><subject>Alanine</subject><subject>Amino Acid Substitution</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Antiviral agents</subject><subject>Arginine</subject><subject>Aspartic acid</subject><subject>Biology</subject><subject>Blotting, Western</subject><subject>Bonding</subject><subject>Capsid protein</subject><subject>Capsid Proteins - genetics</subject><subject>Capsid Proteins - metabolism</subject><subject>Chain dynamics</subject><subject>Disease resistance</subject><subject>Dynamic structural analysis</subject><subject>Gene expression</subject><subject>Genomics</subject><subject>Glutamic acid</subject><subject>Glutamine</subject><subject>Helices</subject><subject>HIV</subject><subject>HIV Infections - genetics</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - genetics</subject><subject>HIV-1 - immunology</subject><subject>HIV-2 - genetics</subject><subject>HIV-2 - growth & development</subject><subject>HIV-2 - immunology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Hydrogen</subject><subject>Hydrogen bonds</subject><subject>Hydrophobicity</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Kinases</subject><subject>Macaca fascicularis</subject><subject>Models, Molecular</subject><subject>Molecular dynamics</subject><subject>Molecular Dynamics Simulation</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutation</subject><subject>Proline</subject><subject>Protein Conformation</subject><subject>Protein structure</subject><subject>Proteins</subject><subject>Proteins - chemistry</subject><subject>Proteins - genetics</subject><subject>Proteins - immunology</subject><subject>Residues</subject><subject>Ring structures</subject><subject>Sensitivity</subject><subject>Simian Immunodeficiency Virus - genetics</subject><subject>Simian Immunodeficiency Virus - growth & development</subject><subject>Simian Immunodeficiency Virus - immunology</subject><subject>Simulation</subject><subject>Studies</subject><subject>Viral infections</subject><subject>Virus Replication</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNp1kt1u1DAQhSMEoqXwBggscb1LbMdOcoNUVfysVISE9t6a2OOtV4kdbGfLPggPwovwTGTZbdVe4Bv_nfPNaHSK4jUtl5TX9P02TNFDvxyDx2VZMlbX7ZPinLacLSQr-dMH57PiRUrbshS8kfJ5ccZow1pB6Xnx65Ik5zc9EhicDwS0MyRYcjMN4IkbhskHg9Zph17vyc7FKZG8H5EwomFMs3qMIaPzBKxFnRPRwdsQB8gu-AMq3waCPzMeuiV9CGMi4M0BNd8T-uSy27m8JzmQ9ffVV_Hn98vimYU-4avTflGsP31cX31ZXH_7vLq6vF5owURecCEb2nCLkoFtOTcoK6it0KaytLNgtQU0VDQto6aSKLkRHVSG0rbj0PKL4u0RO_YhqdNAk6K8lIxKTutZsToqTICtGqMbIO5VAKf-PYS4URCz0z0qoB1qrDXrUFTc6rk-gu4akPMSopxZH07Vpm5Ao9HneQKPoI9_vLtRm7BTnFaiFmwGvDsBYvgxYcr_abk6qnQMKUW09xVoqQ7JuXOpQ3LUKTmz7c3D7u5Nd1HhfwEdJ8d5</recordid><startdate>2011</startdate><enddate>2011</enddate><creator>Miyamoto, Tadashi</creator><creator>Yokoyama, Masaru</creator><creator>Kono, Ken</creator><creator>Shioda, Tatsuo</creator><creator>Sato, Hironori</creator><creator>Nakayama, Emi E</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>2011</creationdate><title>A single amino acid of human immunodeficiency virus type 2 capsid protein affects conformation of two external loops and viral sensitivity to TRIM5α</title><author>Miyamoto, Tadashi ; Yokoyama, Masaru ; Kono, Ken ; Shioda, Tatsuo ; Sato, Hironori ; Nakayama, Emi E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-3568183fe62af933de64a7f5cd4f1bfafcfaed158921d46e63d5ba4d119b3a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acids</topic><topic>Alanine</topic><topic>Amino Acid Substitution</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Antiviral agents</topic><topic>Arginine</topic><topic>Aspartic acid</topic><topic>Biology</topic><topic>Blotting, Western</topic><topic>Bonding</topic><topic>Capsid protein</topic><topic>Capsid Proteins - 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To elucidate details of the interaction between the CA and TRIM5α, we generated mutant HIV-2 viruses, each carrying one of the remaining 17 possible amino acid residues, and examined their sensitivity to CM TRIM5α-mediated restriction. Results showed that hydrophobic residues or those with ring structures were associated with sensitivity, while those with small side chains or amide groups conferred resistance. Molecular dynamics simulation study revealed a structural basis for the differential TRIM5α sensitivities. The mutations at position 120 in the loop between helices 6 and 7 (L6/7) affected conformation of the neighboring loop between helices 4 and 5 (L4/5), and sensitive viruses had a common L4/5 conformation. In addition, the common L4/5 structures of the sensitive viruses were associated with a decreased probability of hydrogen bond formation between the 97th aspartic acid in L4/5 and the 119th arginine in L6/7. When we introduced aspartic acid-to-alanine substitution at position 97 (D97A) of the resistant virus carrying glutamine at position 120 to disrupt hydrogen bond formation, the resultant virus became moderately sensitive. Interestingly, the virus carrying glutamic acid at position 120 showed resistance, while its predicted L4/5 conformation was similar to those of sensitive viruses. The D97A substitution failed to alter the resistance of this particular virus, indicating that the 120th amino acid residue itself is also involved in sensitivity regardless of the L4/5 conformation. These results suggested that a hydrogen bond between the L4/5 and L6/7 modulates the overall structure of the exposed surface of the CA, but the amino acid residue at position 120 is also directly involved in CM TRIM5α recognition.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21829511</pmid><doi>10.1371/journal.pone.0022779</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1306216317 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids Alanine Amino Acid Substitution Amino acids Animals Antiviral agents Arginine Aspartic acid Biology Blotting, Western Bonding Capsid protein Capsid Proteins - genetics Capsid Proteins - metabolism Chain dynamics Disease resistance Dynamic structural analysis Gene expression Genomics Glutamic acid Glutamine Helices HIV HIV Infections - genetics HIV Infections - immunology HIV Infections - virology HIV-1 - genetics HIV-1 - immunology HIV-2 - genetics HIV-2 - growth & development HIV-2 - immunology Human immunodeficiency virus Humans Hydrogen Hydrogen bonds Hydrophobicity Infections Infectious diseases Kinases Macaca fascicularis Models, Molecular Molecular dynamics Molecular Dynamics Simulation Mutagenesis, Site-Directed Mutation Proline Protein Conformation Protein structure Proteins Proteins - chemistry Proteins - genetics Proteins - immunology Residues Ring structures Sensitivity Simian Immunodeficiency Virus - genetics Simian Immunodeficiency Virus - growth & development Simian Immunodeficiency Virus - immunology Simulation Studies Viral infections Virus Replication Viruses |
| title | A single amino acid of human immunodeficiency virus type 2 capsid protein affects conformation of two external loops and viral sensitivity to TRIM5α |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T10%3A26%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20single%20amino%20acid%20of%20human%20immunodeficiency%20virus%20type%202%20capsid%20protein%20affects%20conformation%20of%20two%20external%20loops%20and%20viral%20sensitivity%20to%20TRIM5%CE%B1&rft.jtitle=PloS%20one&rft.au=Miyamoto,%20Tadashi&rft.date=2011&rft.volume=6&rft.issue=7&rft.spage=e22779&rft.pages=e22779-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0022779&rft_dat=%3Cproquest_plos_%3E2900075761%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1306216317&rft_id=info:pmid/21829511&rft_doaj_id=oai_doaj_org_article_a1bece7c2be543fcbfaeacb8a6666550&rfr_iscdi=true |