Structure of native HIV-1 cores and their interactions with IP6 and CypA

DOI: 10.1126/sciadv.abj5715

Authors: Tao Ni (Wellcome Trust Centre for Human Genetics, University of Oxford) , Yanan Zhu (Wellcome Trust Centre for Human Genetics, University of Oxford) , Zhengyi Yang (Diamond Light Source) , Chaoyi Xu (University of Delaware) , Yuriy Chaban (Diamond Light Source) , Tanya Nesterova (University of Delaware) , Jiying Ning (University of Pittsburgh School of Medicine) , Till Böcking (UNSW Sydney) , Michael W. Parker (The University of Melbourne; St. Vincent’s Institute of Medical Research) , Christina Monnie (University of Pittsburgh School of Medicine) , Jinwoo Ahn (University of Pittsburgh School of Medicine) , Juan R. Perilla (University of Delaware) , Peijun Zhang (Wellcome Trust Centre for Human Genetics, University of Oxford; Diamond Light Source; Chinese Academy of Medical Sciences Oxford Institute, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science Advances , VOL 7

State: Published (Approved)
Published: November 2021
Diamond Proposal Number(s): 21004 , 20223

Abstract: The viral capsid plays essential roles in HIV replication and is a major platform engaging host factors. To overcome challenges in study native capsid structure, we used the perfringolysin O to perforate the membrane of HIV-1 particles, thus allowing host proteins and small molecules to access the native capsid while improving cryo–electron microscopy image quality. Using cryo–electron tomography and subtomogram averaging, we determined the structures of native capsomers in the presence and absence of inositol hexakisphosphate (IP6) and cyclophilin A and constructed an all-atom model of a complete HIV-1 capsid. Our structures reveal two IP6 binding sites and modes of cyclophilin A interactions. Free energy calculations substantiate the two binding sites at R18 and K25 and further show a prohibitive energy barrier for IP6 to pass through the pentamer. Our results demonstrate that perfringolysin O perforation is a valuable tool for structural analyses of enveloped virus capsids and interactions with host cell factors.

Diamond Keywords: Human Immunodeficiency Virus (HIV); Viruses

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond , Krios II-Titan Krios II at Diamond , Krios IV-Titan Krios IV at Diamond

Added On: 21/11/2021 20:04

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Imaging Tomography Cryo Electron Tomography (Cryo ET)