Herpes simplex virus type 1 (HSV-1) packages its genome via the portal protein, pUL6, a dodecamer... more Herpes simplex virus type 1 (HSV-1) packages its genome via the portal protein, pUL6, a dodecameric ring at one of the capsid’s twelve vertices. While the portal has been visualized in mature capsids, we aimed to describe it in procapsids to elucidate its role in assembly and maturation. Using cryo-electron tomography, we compared procapsids and empty mature capsids (A-capsids) by subtomogram averaging. The portal is located on the interior surface with its narrower end facing outwards in contact with the capsid shell. The portal is embedded in the underlying scaffold, consistent with assembly initiating on a portal-scaffold complex. Maturation involves angularization of the capsid shell, with an accompanying outward movement of the vertices. In A-capsids, the portal translocates further than the surrounding capsomers, enhancing and presumably strengthening its contacts with the capsid shell. We also found a density overlying and offset from the portal vertex corresponding to the ex...
Proceedings of the National Academy of Sciences, Dec 12, 2006
Influenza virus remains a global health threat, with millions of infections annually and the impe... more Influenza virus remains a global health threat, with millions of infections annually and the impending threat that a strain of avian influenza may develop into a human pandemic. Despite its importance as a pathogen, little is known about the virus structure, in part because of its intrinsic structural variability (pleiomorphy): the primary distinction is between spherical and elongated particles, but both vary in size. Pleiomorphy has thwarted structural analysis by image reconstruction of electron micrographs based on averaging ...
Proceedings of the National Academy of Sciences, Dec 12, 2006
Influenza virus remains a global health threat, with millions of infections annually and the impe... more Influenza virus remains a global health threat, with millions of infections annually and the impending threat that a strain of avian influenza may develop into a human pandemic. Despite its importance as a pathogen, little is known about the virus structure, in part because of its intrinsic structural variability (pleiomorphy): the primary distinction is between spherical and elongated particles, but both vary in size. Pleiomorphy has thwarted structural analysis by image reconstruction of electron micrographs based on averaging ...
HIV-1 Rev protein mediates the nuclear export of viral RNA genomes. To do so, Rev oligomerizes co... more HIV-1 Rev protein mediates the nuclear export of viral RNA genomes. To do so, Rev oligomerizes cooperatively onto an RNA motif, the Rev response element (RRE), forming a complex that engages with the host nuclear export machinery. To better understand Rev oligomerization, we determined four crystal structures of Rev N-terminal domain dimers, which show that they can pivot about their dyad axis, giving crossing angles of 90° to 140°. In parallel, we performed cryoelectron microscopy of helical Rev filaments. Filaments vary from 11 to 15 nm in width, reflecting variations in dimer crossing angle. These structures contain additional density, indicating that C-terminal domains become partially ordered in the context of filaments. This conformational variability may be exploited in the assembly of RRE/Rev complexes. Our data also revealed a third interface between Revs, which offers an explanation for how the arrangement of Rev subunits adapts to the "A"-shaped architecture of ...
The large number of sequences available for the aquaporin family represents a valuable source of ... more The large number of sequences available for the aquaporin family represents a valuable source of information to incorporate into three-dimensional structure determination. Phylogenetic analysis was used to define type sequences to avoid extreme over-representation of some subfamilies, and as a measure of the quality of multiple sequence alignment. Inspection of the sequence alignment suggested eight conserved segments that define the core architecture of six transmembrane helices and two functional loops, B and E, projecting into the plane of the membrane. The sum of the core segments and the minimum lengths of the interlinking loops constitute the 208 residues necessary to satisfy the aquaporin architecture. Analysis of hydrophobic and conservation periodicity and of correlated mutations across the alignment indicated the likely assignment and orientation of the helices in the bilayer. This assignment is examined with respect to the structure of the erythrocyte aquaporin 1 determined by electron crystallography. The aquaporin 1 tetramer is described as three rings of helices, each ring with a different exposure to the lipid environment. The sequence analysis clearly suggests that two helices are exposed along their whole lengths, two helices are exposed only at their N termini, and two helices are not exposed to lipid. It is further proposed that, besides loops B and E, the highly conserved motifs on helices 1 and 4, ExxxTxxF/L, could line the water channel.
Advances in experimental medicine and biology, 2012
Herpesviruses, a family of animal viruses with large (125-250 kbp) linear DNA genomes, are highly... more Herpesviruses, a family of animal viruses with large (125-250 kbp) linear DNA genomes, are highly diversified in terms of host range; nevertheless, their virions conform to a common architecture. The genome is confined at high density within a thick-walled icosahedral capsid with the uncommon (among viruses, generally) but unvarying triangulation number T = 16. The envelope is a membrane in which some 11 different viral glycoproteins are implanted. Between the capsid and the envelope is a capacious compartment called the tegument that accommodates ∼20-40 different viral proteins (depending on which virus) destined for delivery into a host cell. A strong body of evidence supports the hypothesis that herpesvirus capsids and those of tailed bacteriophages stem from a distant common ancestor, whereas their radically different infection apparatuses - envelope on one hand and tail on the other - reflect subsequent coevolution with divergent hosts. Here we review the molecular components o...
News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society, 1999
How water permeates cellular membranes and what this means for cell functioning and several disea... more How water permeates cellular membranes and what this means for cell functioning and several diseases are now emerging from the study of the aquaporins (AQPs), the water channel family. A combination of sequence analysis, three-dimensional structure determination, and physiology of the AQP family proteins provides a glimpse into the workings of water channels.
Herpes simplex virus type 1 (HSV-1) packages its genome via the portal protein, pUL6, a dodecamer... more Herpes simplex virus type 1 (HSV-1) packages its genome via the portal protein, pUL6, a dodecameric ring at one of the capsid’s twelve vertices. While the portal has been visualized in mature capsids, we aimed to describe it in procapsids to elucidate its role in assembly and maturation. Using cryo-electron tomography, we compared procapsids and empty mature capsids (A-capsids) by subtomogram averaging. The portal is located on the interior surface with its narrower end facing outwards in contact with the capsid shell. The portal is embedded in the underlying scaffold, consistent with assembly initiating on a portal-scaffold complex. Maturation involves angularization of the capsid shell, with an accompanying outward movement of the vertices. In A-capsids, the portal translocates further than the surrounding capsomers, enhancing and presumably strengthening its contacts with the capsid shell. We also found a density overlying and offset from the portal vertex corresponding to the ex...
Proceedings of the National Academy of Sciences, Dec 12, 2006
Influenza virus remains a global health threat, with millions of infections annually and the impe... more Influenza virus remains a global health threat, with millions of infections annually and the impending threat that a strain of avian influenza may develop into a human pandemic. Despite its importance as a pathogen, little is known about the virus structure, in part because of its intrinsic structural variability (pleiomorphy): the primary distinction is between spherical and elongated particles, but both vary in size. Pleiomorphy has thwarted structural analysis by image reconstruction of electron micrographs based on averaging ...
Proceedings of the National Academy of Sciences, Dec 12, 2006
Influenza virus remains a global health threat, with millions of infections annually and the impe... more Influenza virus remains a global health threat, with millions of infections annually and the impending threat that a strain of avian influenza may develop into a human pandemic. Despite its importance as a pathogen, little is known about the virus structure, in part because of its intrinsic structural variability (pleiomorphy): the primary distinction is between spherical and elongated particles, but both vary in size. Pleiomorphy has thwarted structural analysis by image reconstruction of electron micrographs based on averaging ...
HIV-1 Rev protein mediates the nuclear export of viral RNA genomes. To do so, Rev oligomerizes co... more HIV-1 Rev protein mediates the nuclear export of viral RNA genomes. To do so, Rev oligomerizes cooperatively onto an RNA motif, the Rev response element (RRE), forming a complex that engages with the host nuclear export machinery. To better understand Rev oligomerization, we determined four crystal structures of Rev N-terminal domain dimers, which show that they can pivot about their dyad axis, giving crossing angles of 90° to 140°. In parallel, we performed cryoelectron microscopy of helical Rev filaments. Filaments vary from 11 to 15 nm in width, reflecting variations in dimer crossing angle. These structures contain additional density, indicating that C-terminal domains become partially ordered in the context of filaments. This conformational variability may be exploited in the assembly of RRE/Rev complexes. Our data also revealed a third interface between Revs, which offers an explanation for how the arrangement of Rev subunits adapts to the "A"-shaped architecture of ...
The large number of sequences available for the aquaporin family represents a valuable source of ... more The large number of sequences available for the aquaporin family represents a valuable source of information to incorporate into three-dimensional structure determination. Phylogenetic analysis was used to define type sequences to avoid extreme over-representation of some subfamilies, and as a measure of the quality of multiple sequence alignment. Inspection of the sequence alignment suggested eight conserved segments that define the core architecture of six transmembrane helices and two functional loops, B and E, projecting into the plane of the membrane. The sum of the core segments and the minimum lengths of the interlinking loops constitute the 208 residues necessary to satisfy the aquaporin architecture. Analysis of hydrophobic and conservation periodicity and of correlated mutations across the alignment indicated the likely assignment and orientation of the helices in the bilayer. This assignment is examined with respect to the structure of the erythrocyte aquaporin 1 determined by electron crystallography. The aquaporin 1 tetramer is described as three rings of helices, each ring with a different exposure to the lipid environment. The sequence analysis clearly suggests that two helices are exposed along their whole lengths, two helices are exposed only at their N termini, and two helices are not exposed to lipid. It is further proposed that, besides loops B and E, the highly conserved motifs on helices 1 and 4, ExxxTxxF/L, could line the water channel.
Advances in experimental medicine and biology, 2012
Herpesviruses, a family of animal viruses with large (125-250 kbp) linear DNA genomes, are highly... more Herpesviruses, a family of animal viruses with large (125-250 kbp) linear DNA genomes, are highly diversified in terms of host range; nevertheless, their virions conform to a common architecture. The genome is confined at high density within a thick-walled icosahedral capsid with the uncommon (among viruses, generally) but unvarying triangulation number T = 16. The envelope is a membrane in which some 11 different viral glycoproteins are implanted. Between the capsid and the envelope is a capacious compartment called the tegument that accommodates ∼20-40 different viral proteins (depending on which virus) destined for delivery into a host cell. A strong body of evidence supports the hypothesis that herpesvirus capsids and those of tailed bacteriophages stem from a distant common ancestor, whereas their radically different infection apparatuses - envelope on one hand and tail on the other - reflect subsequent coevolution with divergent hosts. Here we review the molecular components o...
News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society, 1999
How water permeates cellular membranes and what this means for cell functioning and several disea... more How water permeates cellular membranes and what this means for cell functioning and several diseases are now emerging from the study of the aquaporins (AQPs), the water channel family. A combination of sequence analysis, three-dimensional structure determination, and physiology of the AQP family proteins provides a glimpse into the workings of water channels.
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Papers by Bernard Heymann