Author
W. Hayes McDonald
Other affiliations: Howard Hughes Medical Institute, University of British Columbia, University of Tennessee ...read more
Bio: W. Hayes McDonald is an academic researcher from Vanderbilt University. The author has contributed to research in topics: Proteome & Schizosaccharomyces. The author has an hindex of 51, co-authored 110 publications receiving 11219 citations. Previous affiliations of W. Hayes McDonald include Howard Hughes Medical Institute & University of British Columbia.
Topics: Proteome, Schizosaccharomyces, Gene, Phosphorylation, Ubiquitin
Papers published on a yearly basis
Papers
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TL;DR: These findings reveal an unexpected coupling between substrate deubiquitination and degradation and suggest a unifying rationale for the presence of the lid in eukaryotic proteasomes.
Abstract: The 26S proteasome mediates degradation of ubiquitin-conjugated proteins. Although ubiquitin is recycled from proteasome substrates, the molecular basis of deubiquitination at the proteasome and its relation to substrate degradation remain unknown. The Rpn11 subunit of the proteasome lid subcomplex contains a highly conserved Jab1/MPN domain–associated metalloisopeptidase (JAMM) motif—EX_(n)HXHX_(10)D. Mutation of the predicted active-site histidines to alanine (rpn11AXA) was lethal and stabilized ubiquitin pathway substrates in yeast. Rpn11^(AXA) mutant proteasomes assembled normally but failed to either deubiquitinate or degrade ubiquitinated Sic1 in vitro. Our findings reveal an unexpected coupling between substrate deubiquitination and degradation and suggest a unifying rationale for the presence of the lid in eukaryotic proteasomes.
1,023 citations
Virginia Tech1, Lawrence Berkeley National Laboratory2, Joint Genome Institute3, Wageningen University and Research Centre4, University of Warwick5, Imperial College London6, University of California, Berkeley7, Cornell University8, Ohio Agricultural Research and Development Center9, Agriculture and Agri-Food Canada10, Agricultural Research Service11, Lawrence Livermore National Laboratory12, North Carolina State University13, University of Tennessee14, Oak Ridge National Laboratory15, University of California, Merced16, University of Queensland17, Wilkes University18, Bowling Green State University19, Hokkaido University20
TL;DR: Comparison of the two species' genomes reveals a rapid expansion and diversification of many protein families associated with plant infection such as hydrolases, ABC transporters, protein toxins, proteinase inhibitors, and, in particular, a superfamily of 700 proteins with similarity to known oömycete avirulence genes.
Abstract: Draft genome sequences have been determined for the soybean pathogen Phytophthora sojae and the sudden oak death pathogen Phytophthora ramorum. Oomycetes such as these Phytophthora species share the kingdom Stramenopila with photosynthetic algae such as diatoms, and the presence of many Phytophthora genes of probable phototroph origin supports a photosynthetic ancestry for the stramenopiles. Comparison of the two species' genomes reveals a rapid expansion and diversification of many protein families associated with plant infection such as hydrolases, ABC transporters, protein toxins, proteinase inhibitors, and, in particular, a superfamily of 700 proteins with similarity to known oomycete avirulence genes.
1,016 citations
TL;DR: Infestation of Sirt3⁻/⁻ MEFs with lenti-MnSOD(K122-R) inhibited in vitro immortalization by an oncogene (Ras), inhibited IR-induced genomic instability, and decreased mitochondrial superoxide, suggesting acetylation directly regulates function.
811 citations
TL;DR: This work describes a process for the analysis of posttranslational modifications that is simple, robust, general, and can be applied to complicated protein mixtures and lens tissue from a patient with congenital cataracts.
Abstract: Large-scale genomics has enabled proteomics by creating sequence infrastructures that can be used with mass spectrometry data to identify proteins. Although protein sequences can be deduced from nucleotide sequences, posttranslational modifications to proteins, in general, cannot. We describe a process for the analysis of posttranslational modifications that is simple, robust, general, and can be applied to complicated protein mixtures. A protein or protein mixture is digested by using three different enzymes: one that cleaves in a site-specific manner and two others that cleave nonspecifically. The mixture of peptides is separated by multidimensional liquid chromatography and analyzed by a tandem mass spectrometer. This approach has been applied to modification analyses of proteins in a simple protein mixture, Cdc2p protein complexes isolated through the use of an affinity tag, and lens tissue from a patient with congenital cataracts. Phosphorylation sites have been detected with known stoichiometry of as low as 10%. Eighteen sites of four different types of modification have been detected on three of the five proteins in a simple mixture, three of which were previously unreported. Three proteins from Cdc2p isolated complexes yielded eight sites containing three different types of modifications. In the lens tissue, 270 proteins were identified, and 11 different crystallins were found to contain a total of 73 sites of modification. Modifications identified in the crystallin proteins included Ser, Thr, and Tyr phosphorylation, Arg and Lys methylation, Lys acetylation, and Met, Tyr, and Trp oxidations. The method presented will be useful in discovering co- and posttranslational modifications of proteins.
584 citations
TL;DR: It is reported that Mus81 and an associated protein Eme1 are components of an endonuclease that resolves Holliday junctions into linear duplex products and constitute strong evidence that Mus 81 and Eme 1 are subunits of a nuclear Holliday junction resolvase.
534 citations
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TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.
9,980 citations
TL;DR: This work developed a new gene prediction algorithm called Prodigal (PROkaryotic DYnamic programming Gene-finding ALgorithm), which achieved good results compared to existing methods, and it is believed it will be a valuable asset to automated microbial annotation pipelines.
Abstract: The quality of automated gene prediction in microbial organisms has improved steadily over the past decade, but there is still room for improvement. Increasing the number of correct identifications, both of genes and of the translation initiation sites for each gene, and reducing the overall number of false positives, are all desirable goals. With our years of experience in manually curating genomes for the Joint Genome Institute, we developed a new gene prediction algorithm called Prodigal (PROkaryotic DYnamic programming Gene-finding ALgorithm). With Prodigal, we focused specifically on the three goals of improved gene structure prediction, improved translation initiation site recognition, and reduced false positives. We compared the results of Prodigal to existing gene-finding methods to demonstrate that it met each of these objectives. We built a fast, lightweight, open source gene prediction program called Prodigal http://compbio.ornl.gov/prodigal/
. Prodigal achieved good results compared to existing methods, and we believe it will be a valuable asset to automated microbial annotation pipelines.
7,157 citations
TL;DR: The ability of mass spectrometry to identify and, increasingly, to precisely quantify thousands of proteins from complex samples can be expected to impact broadly on biology and medicine.
Abstract: Recent successes illustrate the role of mass spectrometry-based proteomics as an indispensable tool for molecular and cellular biology and for the emerging field of systems biology. These include the study of protein-protein interactions via affinity-based isolations on a small and proteome-wide scale, the mapping of numerous organelles, the concurrent description of the malaria parasite genome and proteome, and the generation of quantitative protein profiles from diverse species. The ability of mass spectrometry to identify and, increasingly, to precisely quantify thousands of proteins from complex samples can be expected to impact broadly on biology and medicine.
6,597 citations
TL;DR: This work speculates on the reasons behind this large discrepancy between the expectations arising from proteomics and the realities of clinical diagnostics and suggests approaches by which protein-disease associations may be more effectively translated into diagnostic tools in the future.
4,062 citations
TL;DR: This work isolated active Wnt molecules, including the product of the mouse Wnt3a gene, and found the proteins to be palmitoylated on a conserved cysteine, indicating that the lipid is important for signalling.
Abstract: Wnt signalling is involved in numerous events in animal development, including the proliferation of stem cells and the specification of the neural crest. Wnt proteins are potentially important reagents in expanding specific cell types, but in contrast to other developmental signalling molecules such as hedgehog proteins and the bone morphogenetic proteins, Wnt proteins have never been isolated in an active form. Although Wnt proteins are secreted from cells, secretion is usually inefficient and previous attempts to characterize Wnt proteins have been hampered by their high degree of insolubility. Here we have isolated active Wnt molecules, including the product of the mouse Wnt3a gene. By mass spectrometry, we found the proteins to be palmitoylated on a conserved cysteine. Enzymatic removal of the palmitate or site-directed and natural mutations of the modified cysteine result in loss of activity, and indicate that the lipid is important for signalling. The purified Wnt3a protein induces self-renewal of haematopoietic stem cells, signifying its potential use in tissue engineering.
2,323 citations