Biomedical subjects

David Gene Morgan

Publications and source records attributed to David Gene Morgan.

3 recordsLinked to original sources

PubMed2006

Efficient implementation of a filtered back-projection algorithm using a voxel-by-voxel approach.

The large amount of image data necessary for high-resolution 3D reconstruction of macromolecular assemblies leads to significant increases in the computational time. One of the most time consuming operations is 3D density map reconstruction, and software optimization can greatly reduce the time required for any given structural study. The majority of algorithms proposed for improving the computational effectiveness of a 3D reconstruction are based on a ray-by-ray projection of each image into the reconstructed volume. In this paper, we propose a novel fast implementation of the "filtered back-projection" algorithm based on a voxel-by-voxel principle. Our version of this implementation has been exhaustively tested using both model and real data. We compared 3D reconstructions obtained by the new approach with results obtained by the filtered Back-Projections algorithm and the Fourier-Bessel algorithm commonly used for reconstructing icosahedral viruses. These computational experiments demonstrate the robustness, reliability, and efficiency of this approach.

Algorithms↗

PubMed2002

Structure of the mammalian ribosome-channel complex at 17A resolution.

The co-translational translocation of proteins into the endoplasmic reticulum (ER) lumen and the biogenesis of membrane proteins require ribosome binding to a membrane channel formed by the Sec61p complex. We now report the 17A structure of a mammalian ribosome-channel complex derived from ER membranes. Atomic models of the ribosomal subunits were aligned to the programmed ribosome from Thermus thermophilus, to provide a common reference frame. The T.thermophilus ribosome, and by extension all known high resolution subunit models, were then docked within our map of the ribosome-channel complex. The structure shows that the ribosome contains a putative tRNA in the exit site, and a comparison with a non-programmed, yeast ribosome suggests that the L1 stalk may function as a gate in the tRNA exit path. We have localized six major expansion segments in the large subunit of the vertebrate ribosome including ES27, and suggest a function for ES30. The large ribosomal subunit is linked to the channel by four connections. We identified regions in the large subunit rRNA and four proteins that may help form the connections. These regions of the ribosome probably serve as a template to guide the assembly of the asymmetric translocation channel. Three of the connections form a picket fence that separates the putative translocation pore from the attachment site of an additional membrane component. The ribosome-channel connections also create an open junction that would allow egress of a nascent chain into the cytosol. At a threshold that is appropriate for the entire complex, the channel is rather solid and the lumenal half of the putative translocation pore is closed. These data suggest that the flow of small molecules across the membrane may be impeded by the channel itself, rather than the ribosome-channel junction.

Animals↗

PubMed2002

Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation.

The apoptosome is an Apaf-1 cytochrome c complex that activates procaspase-9. The three-dimensional structure of the apoptosome has been determined at 27 A resolution, to reveal a wheel-like particle with 7-fold symmetry. Molecular modeling was used to identify the caspase recruitment and WD40 domains within the apoptosome and to infer likely positions of the CED4 homology motif and cytochrome c. This analysis suggests a plausible role for cytochrome c in apoptosome assembly. In a subsequent structure, a noncleavable mutant of procaspase-9 was localized to the central region of the apoptosome. This complex promotes the efficient activation of procaspase-3. Therefore, the cleavage of procaspase-9 is not required to form an active cell death complex.

Amino Acid Motifs↗