Human rhinovirus 3 at 3.0 å resolution

Zhao, Rui; Pevear, Daniel C.; Kremer, Marcia J.; Giranda, Vincent L.; Kofron, J.; Kühn, Richard; Rossmann, Michael G.

doi:10.1016/s0969-2126(96)00128-1

Cited by 108 publications

(72 citation statements)

References 67 publications

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“…The pentagonal bipyramid conformation is common for Ca 2+ -binding proteins (Fig. S7), for example, the canonical EF-hand motif, the HRV (rhinovirus) protein (34,35), and the Ca 2+ ATPase (36). Ion selectivity is the result of highly specific ion binding to the permeation pathway (18), and we propose that the double carboxylate rings of MCU generate strong ion affinity through positive cooperativity.…”

Section: +mentioning

confidence: 90%

Ion and inhibitor binding of the double-ring ion selectivity filter of the mitochondrial calcium uniporter

Cao

Wang

Cui

et al. 2017

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

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The calcium (Ca 2+ ) uniporter of mitochondria is a holocomplex consisting of the Ca 2+ -conducting channel, known as mitochondrial calcium uniporter (MCU), and several accessory and regulatory components. A previous electrophysiology study found that the uniporter has high Ca 2+ selectivity and conductance and this depends critically on the conserved amino acid sequence motif, DXXE (Asp-X-X-Glu) of MCU. A recent NMR structure of the MCU channel from Caenorhabditis elegans revealed that the DXXE forms two parallel carboxylate rings at the channel entrance that seem to serve as the ion selectivity filter, although direct ion interaction of this structural motif has not been addressed. Here, we use a paramagnetic probe, manganese (Mn 2+ ), to investigate ion and inhibitor binding of this putative selectivity filter. Our paramagnetic NMR data show that mutants with a single carboxylate ring, NXXE (Asn-X-X-Glu) and DXXQ (Asp-X-X-Gln), each can bind Mn 2+ specifically, whereas in the WT the two rings bind Mn 2+ cooperatively, resulting in ∼1,000-fold higher apparent affinity. Ca 2+ can specifically displace the bound Mn 2+ at the DXXE site in the channel. Furthermore, titrating the sample with the known channel inhibitor ruthenium 360 (Ru360) can displace Mn 2+ binding from the solventaccessible Asp site but not the inner Glu site. The NMR titration data, together with structural analysis of the DXXE motif and molecular dynamics simulation, indicate that the double carboxylate rings at the apex of the MCU pore constitute the ion selectivity filter and that Ru360 directly blocks ion entry into the filter by binding to the outer carboxylate ring.) uptake by mitochondria is a long-known physiological phenomenon that is important for regulating various cellular activities such as aerobic metabolism and cell death (1-3). This uptake of Ca 2+ is achieved by a Ca 2+ uniporter whose activity can be blocked by ruthenium red (RuR) or ruthenium 360 (Ru360) (4). It was later shown by patch-clamping the inner mitochondrial membrane that this uniporter achieves remarkably high Ca 2+ conductance and selectivity (5). Only about 5 y ago was the molecular identity of the channel component of the uniporter identified using integrative genomics approaches (6, 7). This channel is commonly referred to as the mitochondrial calcium uniporter (MCU). In metazoans, however, the uniporter is much more complex than just the pore-forming subunit; it is a holocomplex (also called a uniplex) containing other regulatory components. Among them, the single-pass transmembrane (TM) protein EMRE (Essential MCU REgulator) is absolutely required for the MCU to conduct ions (8). Two soluble components in the intermembrane space, MICU1 and MICU2, are Ca 2+ -sensing proteins that gate the activity of MCU based on outside Ca 2+ concentrations through EMRE (9-12). The current consensus is that the minimum requirements for uniporter-mediated Ca 2+ flux in metazoans are MCU and EMRE, whereas in lower organisms such as Dictyostelium that lack EMRE, MCU i...

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Section: +mentioning

confidence: 90%

Ion and inhibitor binding of the double-ring ion selectivity filter of the mitochondrial calcium uniporter

Cao

Wang

Cui

et al. 2017

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

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“…RV-B14 was grown in HeLa-H1 (ATCC CRL195) cells and purified as described previously (42,43). Briefly, cells were infected by RV-B14 (multiplicity of infection = 2) for 24-36 h until complete cytopathic effect was observed.…”

Section: Methodsmentioning

confidence: 99%

Antibody-induced uncoating of human rhinovirus B14

Dong

Liu

Jiang

et al. 2017

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

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Rhinoviruses (RVs) are the major causes of common colds in humans. They have a nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here we report that the antigenbinding (Fab) fragment of a neutralizing antibody (C5) can trigger genome release from RV-B14 to form emptied particles and neutralize virus infection. Using cryo-electron microscopy, structures of the C5 Fab in complex with the full and emptied particles have been determined at 2.3 Å and 3.0 Å resolution, respectively. Each of the 60 Fab molecules binds primarily to a region on viral protein 3 (VP3). Binding of the C5 Fabs to RV-B14 results in significant conformational changes around holes in the capsid through which the viral RNA might exit. These results are so far the highest resolution view of an antibody-virus complex and elucidate a mechanism whereby antibodies neutralize RVs and related viruses by inducing virus uncoating.rhinovirus | antibody | cryo-electron microscopy | genome release | atomic structure

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“…Since then, structures of several other picornaviruses have been described (1,34,35,41,48,56,62,(65)(66)(67)84,85,104,112,121,122). The protein shell of the virion is composed of 60 copies of the 4 capsid proteins, VP1, VP2, VP3, and VP4, that are arranged on an icosahedral surface.…”

Section: The Virionmentioning

confidence: 99%

Poliovirus Cell Entry: Common Structural Themes in Viral Cell Entry Pathways

Hogle

2002

Annu. Rev. Microbiol.

313

305

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Structural studies of polio-and closely related viruses have provided a series of snapshots along their cell entry pathways. Based on the structures and related kinetic, biochemical, and genetic studies, we have proposed a model for the cell entry pathway for polio-and closely related viruses. In this model a maturation cleavage of a capsid protein precursor locks the virus in a metastable state, and the receptor acts like a transition-state catalyst to overcome an energy barrier and release the mature virion from the metastable state. This initiates a series of conformational changes that allow the virus to attach to membranes, form a pore, and finally release its RNA genome into the cytoplasm. This model has striking parallels with emerging models for the maturation and cell entry of more complex enveloped viruses such as influenza virus and HIV.

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Human rhinovirus 3 at 3.0 å resolution

Cited by 108 publications

References 67 publications

Ion and inhibitor binding of the double-ring ion selectivity filter of the mitochondrial calcium uniporter

Ion and inhibitor binding of the double-ring ion selectivity filter of the mitochondrial calcium uniporter

Antibody-induced uncoating of human rhinovirus B14

Poliovirus Cell Entry: Common Structural Themes in Viral Cell Entry Pathways

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