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Basic Characteristics of Mutations
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Mutation Site
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T371I |
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Mutation Site Sentence
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Fig. 1. CryoET and subtomogram averaging of Gag T8I assemblies and VLPs. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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Gag |
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Standardized Encoding Gene
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Gag
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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Gag |
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Location
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- |
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Literature Information
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PMID
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33863979
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Title
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CryoET structures of immature HIV Gag reveal six-helix bundle
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Author
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Mendonca L,Sun D,Ning J,Liu J,Kotecha A,Olek M,Frosio T,Fu X,Himes BA,Kleinpeter AB,Freed EO,Zhou J,Aiken C,Zhang P
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Journal
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Communications biology
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Journal Info
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2021 Apr 16;4(1):481
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Abstract
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Gag is the HIV structural precursor protein which is cleaved by viral protease to produce mature infectious viruses. Gag is a polyprotein composed of MA (matrix), CA (capsid), SP1, NC (nucleocapsid), SP2 and p6 domains. SP1, together with the last eight residues of CA, have been hypothesized to form a six-helix bundle responsible for the higher-order multimerization of Gag necessary for HIV particle assembly. However, the structure of the complete six-helix bundle has been elusive. Here, we determined the structures of both Gag in vitro assemblies and Gag viral-like particles (VLPs) to 4.2 A and 4.5 A resolutions using cryo-electron tomography and subtomogram averaging by emClarity. A single amino acid mutation (T8I) in SP1 stabilizes the six-helix bundle, allowing to discern the entire CA-SP1 helix connecting to the NC domain. These structures provide a blueprint for future development of small molecule inhibitors that can lock SP1 in a stable helical conformation, interfere with virus maturation, and thus block HIV-1 infection.
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Sequence Data
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EMD-11894;EMD-11899;EMD-11897;PDB:7ASH;PDB:7ASL;EMD-12287
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