Project 1. Maturation and Assembly

项目 1. 成熟和组装

• 批准号: 10506952
• 负责人: Barbie K. Ganser-Pornillos
• 金额: $ 48.51万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10506952
• 关键词: Binding; Binding Proteins; Binding Sites; Biochemical; Biochemistry; Biological Assay; Biological Metamorphosis; Capsid; Complement; Complex; Computational Technique; Cryoelectron Microscopy; Cytoplasmic Tail; Data; Development; Disulfides; Drug resistance; Enzymes; Generations; Genetic Polymorphism; Goals; HIV; HIV-1; HIV-1 integrase; Individual; Integrase; Integrase Inhibitors; Investigation; Knowledge; Magic; Mediating; Microscopy; Molecular; Mutation; Nucleocapsid; Pathway interactions; Peptide Hydrolases; Play; Process; Proteins; RNA; RNA-Directed DNA Polymerase; RNA-Protein Interaction; Research Personnel; Resistance; Resolution; Ribonucleoproteins; Role; SP1 gene; Series; Site; Structure; Techniques; Testing; Variant; Viral; Viral Matrix Proteins; Viral Proteins; Virion; Virus; Virus Replication; Work; crosslinking and immunoprecipitation sequencing; design; dimer; drug candidate; experimental study; genomic RNA; glycoprotein 41; imaging approach; improved; inhibitor; insight; mutant; novel; particle; pol Gene Products; prevent; solid state nuclear magnetic resonance; viral resistance; virology

Project 1 – HIV-1 Maturation and Assembly The overall goal of this project is to identify and exploit key, potentially druggable complexes and interactions that are present during HIV-1 assembly and maturation, including Gag and its maturation intermediates, the viral ribonucleoprotein (vRNP) complex, and the matrix (MA)-glycoprotein 41 (gp41) cytoplasmic tail interaction. The proposed studies are an integrated effort from 11 PCHPI investigators and four cores (NMR, CryoEM/ET, Computational, and HIV Virology). The specific aims are designed to i) understand the molecular, biochemical, and structural basis for maturation inhibitor (MI) and allosteric integrase inhibitor (ALLINI) activity and resistance pathways; ii) define the organization of RNA and proteins in the viral ribonucleoprotein complex (vRNPs) and at specific stages of maturation; and iii) characterize the interaction between the MA domain of Gag and the cytoplasmic tail of gp41. The structural and mechanistic knowledge gained through the proposed work will inform the development of novel MIs and ALLINIs with improved antiviral potency and potentially guide approaches to inhibit protein interactions in HIV-1 vRNPs and in MA-gp41 complexes.

项目1 - HIV-1的成熟和组装