Structure of Full-Length HIV-1 CA: A Model for the Mature Capsid Lattice

Ganser‐Pornillos, Barbie K.; Cheng, Anchi; Yeager, Mark

doi:10.1016/j.cell.2007.08.018

Cited by 296 publications

(538 citation statements)

References 53 publications

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“…Third, our cryo-EM and cosedimentation experiments reveal that the PRY/SPRY rh domain retains the ability to bind HIV-1 CA helical tubes without breaking the assembly. Importantly, our crystal structure of PRY/SPRY rh , the crystal structure of the HIV-1 CA hexamer lattice (36,51), and the cryo-EM maps of HIV-1 capsid and helical tubes (18,38) together establish a structural framework for further detailed investigation of this lattice-specific interaction.…”

Section: Discussionmentioning

confidence: 82%

Structural insight into HIV-1 capsid recognition by rhesus TRIM5α

Yang

Zhao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Tripartite motif protein isoform 5 alpha (TRIM5α) is a potent antiviral protein that restricts infection by HIV-1 and other retroviruses. TRIM5α recognizes the lattice of the retrovirus capsid through its B30.2 (PRY/SPRY) domain in a species-specific manner. Upon binding, TRIM5α induces premature disassembly of the viral capsid and activates the downstream innate immune response. We have determined the crystal structure of the rhesus TRIM5α PRY/ SPRY domain that reveals essential features for capsid binding. Combined cryo-electron microscopy and biochemical data show that the monomeric rhesus TRIM5α PRY/SPRY, but not the human TRIM5α PRY/SPRY, can bind to HIV-1 capsid protein assemblies without causing disruption of the capsid. This suggests that the PRY/SPRY domain alone constitutes an important pattern-sensing component of TRIM5α that is capable of interacting with viral capsids of different curvatures. Our results provide molecular insights into the mechanisms of TRIM5α-mediated retroviral restriction.

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Section: Discussionmentioning

confidence: 82%

Structural insight into HIV-1 capsid recognition by rhesus TRIM5α

Yang

Zhao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…The self-assembly of the CA proteins has been extensively studied using X-ray, NMR, and cryo-electron microscopy (Cryo-EM). [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Remarkably, a complete atomic model of the capsid was recently obtained by Cryo-EM combined with all-atom simulations. 17 Other theoretical and computational studies [27][28][29][30] also provided important insight into the structure and the assembling process for the HIV capsid.…”

Section: Introductionmentioning

confidence: 99%

Monte Carlo Simulations of HIV Capsid Protein Homodimer

Zhu

Chen

2015

J. Chem. Inf. Model.

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Capsid protein (CA) is the building block of virus coats. To help understand how the HIV CA proteins self-organize into large assemblies of various shapes, here we aim to computationally evaluate the binding affinity and interfaces in a CA homodimer. We model the N-and C-terminal domains (NTD and CTD) of the CA as rigid bodies, and treat the five-residue loop between the two domains as a flexible linker. We adopt a transferrable residue-level coarse-grained energy function to describe the interactions between the protein domains. In seven extensive Monte Carlo simulations with different volumes, a large number of binding / unbinding transitions between the two CA proteins are observed, thus allowing a reliable estimation of the equilibrium probabilities for the dimeric vs. monomeric forms. The obtained dissociation constant for the CA homodimer

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“…Recently, a series of breakthrough studies have revolutionized our understanding of how the CA domains self-assemble to form the mature capsid core of the virus (6)(7)(8), and a pseudoatomic model for the assembled mature core is now available (9). In contrast, much less structural information is available on the immature virus.…”

mentioning

confidence: 99%

Cryo-electron microscopy of tubular arrays of HIV-1 Gag resolves structures essential for immature virus assembly

Bharat

Menendez

Hagen

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

104

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Significance HIV-1 undergoes a two-step assembly process. First, an immature noninfectious particle is assembled, which leaves the infected cell. Second, the structural protein, Gag, is cleaved in the virus by the viral protease, and this leads to formation of the infectious virus. The immature virus particle therefore represents the key intermediate in HIV-1 assembly. There is currently no high-resolution information available on the arrangement of Gag within immature HIV-1. We have assembled part of HIV-1 Gag in vitro to form immature virus-like tubular protein arrays, and have solved a subnanometer-resolution structure of these arrays by using cryo-EM and tomography. This structure reveals interactions of the C-terminal capsid domain of Gag that are critical for HIV-1 assembly.

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Structure of Full-Length HIV-1 CA: A Model for the Mature Capsid Lattice

Cited by 296 publications

References 53 publications

Structural insight into HIV-1 capsid recognition by rhesus TRIM5α

Structural insight into HIV-1 capsid recognition by rhesus TRIM5α

Monte Carlo Simulations of HIV Capsid Protein Homodimer

Cryo-electron microscopy of tubular arrays of HIV-1 Gag resolves structures essential for immature virus assembly

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