Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural insights into inhibitor mechanisms on immature HIV-1 Gag lattice revealed by high-resolution single-particle cryo-EM.
Journal, issue, pages	bioRxiv, Year 2024
Publish date	Oct 9, 2024
Authors	Chunxiang Wu / Megan E Meuser / Juan S Rey / Hamed Meshkin / Rachel Yang / Swapnil Chandrakant Devarkar / Christian Freniere / Jiong Shi / Christopher Aiken / Juan R Perilla / Yong Xiong
PubMed Abstract	HIV-1 inhibitors, such as Bevirimat (BVM) and Lenacapavir (LEN), block the production and maturation of infectious virions. However, their mechanisms remain unclear due to the absence of high- ...HIV-1 inhibitors, such as Bevirimat (BVM) and Lenacapavir (LEN), block the production and maturation of infectious virions. However, their mechanisms remain unclear due to the absence of high-resolution structures for BVM complexes and LEN's structural data being limited to the mature capsid. Utilizing perforated virus-like particles (VLPs) produced from mammalian cells, we developed an approach to determine cryo-electron microscopy (cryo-EM) structures of HIV-1 with inhibitors. This allowed for the first structural determination of the native immature HIV-1 particle with BVM and LEN bound inside the VLPs at high resolutions. Our findings offer a more accurate model of BVM engaging the Gag lattice and, importantly, demonstrate that LEN not only binds the mature capsid but also targets the immature lattice in a distinct manner. The binding of LEN induces a conformational change in the capsid protein (CA) region and alters the architecture of the Gag lattice, which may affect the maturation process. These insights expand our understanding of the inhibitory mechanisms of BVM and LEN on HIV-1 and provide valuable clues for the design of future inhibitors.
External links	bioRxiv / PubMed:39416065 / PubMed Central
Methods	EM (single particle)
Resolution	2.1 - 3.18 Å
Structure data	45975 9cwv EMDB-45975, PDB-9cwv: Gag CA-SP1 immature lattice from intact enveloped virus-like particles Method: EM (single particle) / Resolution: 2.42 Å 46593 9d6c EMDB-46593, PDB-9d6c: Gag CA-SP1 immature lattice bound with Lenacapavir and Bevirimat from enveloped virus like particles Method: EM (single particle) / Resolution: 2.1 Å 46594 9d6d EMDB-46594, PDB-9d6d: Gag CA-SP1 immature lattice bound with Lenacapavir from enveloped virus like particles Method: EM (single particle) / Resolution: 2.18 Å 46595 9d6e EMDB-46595, PDB-9d6e: Gag CA-SP1 immature lattice bound with Bevirimat from enveloped virus like particles Method: EM (single particle) / Resolution: 3.09 Å 46631 9d88 EMDB-46631, PDB-9d88: Gag CA-SP1 immature lattice from enveloped and perforated virus like particles Method: EM (single particle) / Resolution: 3.18 Å 47240 9dwd EMDB-47240, PDB-9dwd: Gag CA-SP1 immature lattice bound with Lenacapavir from enveloped virus like particles (T8I) Method: EM (single particle) / Resolution: 3.13 Å
Chemicals	ChemComp-IHP: INOSITOL HEXAKISPHOSPHATE ChemComp-HOH: WATER ChemComp-QNG: N-[(1S)-1-(3-{4-chloro-3-[(methylsulfonyl)amino]-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl}-6-[3-methyl-3-(methylsulfonyl)but-1-yn-1-yl]pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl]-2-[(3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl]acetamide / medication, antiretroviralYM ChemComp-2I4*: 3alpha-[(3-carboxy-3-methylbutanoyl)oxy]-8alpha,9beta,10alpha,13alpha,17alpha,19beta-lup-20(29)-en-28-oic acid
Source	human immunodeficiency virus type 1 group m subtype b (isolate hxb2) human immunodeficiency virus type 1 (new york-5 isolate)
Keywords	VIRUS LIKE PARTICLE / Gag / CA-SP1 / HIV-1 / Inhibitor / virion assembly / VIRAL PROTEIN