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Biochimica Et Biophysica Acta May 2016This contribution describes the phenotypic differences of yeast peroxisome-deficient mutants (pex mutants). In some cases different phenotypes were reported for yeast... (Review)
Review
This contribution describes the phenotypic differences of yeast peroxisome-deficient mutants (pex mutants). In some cases different phenotypes were reported for yeast mutants deleted in the same PEX gene. These differences are most likely related to the marker proteins and methods used to detect peroxisomal remnants. This is especially evident for pex3 and pex19 mutants, where the localization of receptor docking proteins (Pex13, Pex14) resulted in the identification of peroxisomal membrane remnants, which do not contain other peroxisomal membrane proteins, such as the ring proteins Pex2, Pex10 and Pex12. These structures in pex3 and pex19 cells are the template for peroxisome formation upon introduction of the missing gene. Taken together, these data suggest that in all yeast pex mutants analyzed so far peroxisomes are not formed de novo but use membrane remnant structures as a template for peroxisome formation upon reintroduction of the missing gene. The relevance of this model for peroxisomal membrane protein and lipid sorting to peroxisomes is discussed.
Topics: Animals; Endoplasmic Reticulum; Eukaryotic Cells; Gene Expression Regulation; Humans; Membrane Proteins; Organelle Biogenesis; Peroxins; Peroxisomes; Plants; Protein Isoforms; Protein Structure, Tertiary; Protein Transport; Saccharomyces cerevisiae Proteins; Signal Transduction; Yeasts
PubMed: 26367802
DOI: 10.1016/j.bbamcr.2015.09.008 -
IUBMB Life Aug 2008The target of rapamycin (TOR) is a protein kinase with numerous functions in cell growth control. Some of these functions can be potently inhibited by rapamycin, an... (Review)
Review
The target of rapamycin (TOR) is a protein kinase with numerous functions in cell growth control. Some of these functions can be potently inhibited by rapamycin, an immunosuppressive and potential anticancer drug. TOR exists as part of two functionally distinct protein complexes. The functions of TOR complex 1 (TORC1) are effectively inhibited by rapamycin, but the mechanism for this inhibition remains elusive. The identification of TORC2 and recent reports that rapamycin can inhibit TORC2 functions, in some cases, challenge current models of TOR regulation. This review discusses the latest findings in yeast and mammals on the possible mechanisms that control TOR activity leading to its many cellular functions
Topics: Gene Components; Humans; Models, Biological; Monomeric GTP-Binding Proteins; Multiprotein Complexes; Phosphorylation; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Saccharomyces cerevisiae Proteins; Schizosaccharomyces pombe Proteins; Sirolimus; Species Specificity; Yeasts
PubMed: 18493947
DOI: 10.1002/iub.56 -
Current Opinion in Genetics &... Dec 2015Whilst ∼93% of domain superfamilies appear to be relatively structurally and functionally conserved based on the available data from the CATH-Gene3D domain... (Review)
Review
Whilst ∼93% of domain superfamilies appear to be relatively structurally and functionally conserved based on the available data from the CATH-Gene3D domain classification resource, the remainder are much more diverse. In this review, we consider how domains in some of the most ubiquitous and promiscuous superfamilies have evolved, in particular the plasticity in their functional sites and surfaces which expands the repertoire of molecules they interact with and actions performed on them. To what extent can we identify a core function for these superfamilies which would allow us to develop a 'domain grammar of function' whereby a protein's biological role can be proposed from its constituent domains? Clearly the first step is to understand the extent to which these components vary and how changes in their molecular make-up modifies function.
Topics: Amino Acid Sequence; Models, Molecular; Protein Structure, Tertiary; Proteins
PubMed: 26451979
DOI: 10.1016/j.gde.2015.09.005 -
Biochimica Et Biophysica Acta May 2016Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition... (Review)
Review
Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition that Pex1p shares a conserved ATP-binding domain with p97 and NSF led to the discovery of the extended family of AAA+-type ATPases. So far, four AAA+-type ATPases are related to peroxisome function. Pex6p functions together with Pex1p in peroxisome biogenesis, ATAD1/Msp1p plays a role in membrane protein targeting and a member of the Lon-family of proteases is associated with peroxisomal quality control. This review summarizes the current knowledge on the AAA+-proteins involved in peroxisome biogenesis and function.
Topics: ATPases Associated with Diverse Cellular Activities; Adenosine Triphosphatases; Animals; Eukaryotic Cells; Gene Expression Regulation; Humans; Membrane Proteins; Organelle Biogenesis; Peroxisomes; Plants; Protein Isoforms; Protein Structure, Secondary; Protein Structure, Tertiary; Protein Transport; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction
PubMed: 26453804
DOI: 10.1016/j.bbamcr.2015.10.001 -
The Biochemical Journal Sep 2000Advances in our understanding of the roles of phosphatidylinositol phosphates in controlling cellular functions such as endocytosis, exocytosis and the actin... (Review)
Review
Advances in our understanding of the roles of phosphatidylinositol phosphates in controlling cellular functions such as endocytosis, exocytosis and the actin cytoskeleton have included new insights into the phosphatases that are responsible for the interconversion of these lipids. One of these is an entirely novel class of phosphatase domain found in a number of well characterized proteins. Proteins containing this Sac phosphatase domain include the yeast Saccharomyces cerevisiae proteins Sac1p and Fig4p. The Sac phosphatase domain is also found within the mammalian phosphoinositide 5-phosphatase synaptojanin and the yeast synaptojanin homologues Inp51p, Inp52p and Inp53p. These proteins therefore contain both Sac phosphatase and 5-phosphatase domains. This review describes the Sac phosphatase domain-containing proteins and their actions, with particular reference to the genetic and biochemical insights provided by study of the yeast Saccharomyces cerevisiae.
Topics: Amino Acid Sequence; Flavoproteins; Fungal Proteins; Membrane Proteins; Models, Biological; Models, Chemical; Molecular Sequence Data; Nerve Tissue Proteins; Phosphatidylinositol Phosphates; Phosphoric Monoester Hydrolases; Protein Structure, Tertiary; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid
PubMed: 10947947
DOI: No ID Found -
PLoS Computational Biology Nov 2023We present fast and simple-to-implement measures of the entanglement of protein tertiary structures which are appropriate for highly flexible structure comparison. These...
We present fast and simple-to-implement measures of the entanglement of protein tertiary structures which are appropriate for highly flexible structure comparison. These are performed using the SKMT algorithm, a novel method of smoothing the Cα backbone to achieve a minimal complexity curve representation of the manner in which the protein's secondary structure elements fold to form its tertiary structure. Its subsequent complexity is characterised using measures based on the writhe and crossing number quantities heavily utilised in DNA topology studies, and which have shown promising results when applied to proteins recently. The SKMT smoothing is used to derive empirical bounds on a protein's entanglement relative to its number of secondary structure elements. We show that large scale helical geometries dominantly account for the maximum growth in entanglement of protein monomers, and further that this large scale helical geometry is present in a large array of proteins, consistent across a number of different protein structure types and sequences. We also show how these bounds can be used to constrain the search space of protein structure prediction from small angle x-ray scattering experiments, a method highly suited to determining the likely structure of proteins in solution where crystal structure or machine learning based predictions often fail to match experimental data. Finally we develop a structural comparison metric based on the SKMT smoothing which is used in one specific case to demonstrate significant structural similarity between Rossmann fold and TIM Barrel proteins, a link which is potentially significant as attempts to engineer the latter have in the past produced the former. We provide the SWRITHE interactive python notebook to calculate these metrics.
Topics: Proteins; Algorithms; Protein Structure, Secondary
PubMed: 38011290
DOI: 10.1371/journal.pcbi.1011248 -
Cell May 2003The first structures have been obtained for complexes between CUE domains and monoubiquitin, one by NMR (Kang et al., this issue of Cell) and one by X-ray... (Review)
Review
The first structures have been obtained for complexes between CUE domains and monoubiquitin, one by NMR (Kang et al., this issue of Cell) and one by X-ray crystallography (Prag et al., this issue of Cell), thus providing insights into ubiquitin recognition by CUE domains. Structural comparisons suggest that different CUE surfaces can interact with ubiquitin, indicating that not all CUE domains are created equal.
Topics: Animals; Carrier Proteins; Eukaryotic Cells; Humans; Membrane Proteins; Protein Structure, Secondary; Protein Structure, Tertiary; Saccharomyces cerevisiae Proteins; Signal Transduction; Ubiquitin; Yeasts
PubMed: 12787494
DOI: 10.1016/s0092-8674(03)00398-2 -
Biochimica Et Biophysica Acta 2009Sin3 was isolated over two decades ago as a negative regulator of transcription in budding yeast. Subsequent research has established the protein as a master... (Review)
Review
Sin3 was isolated over two decades ago as a negative regulator of transcription in budding yeast. Subsequent research has established the protein as a master transcriptional scaffold and corepressor capable of transcriptional silencing via associated histone deacetylases (HDACs). The core Sin3-HDAC complex interacts with a wide variety of repressors and corepressors, providing flexibility and expanded specificity in modulating chromatin structure and transcription. As a result, the Sin3/HDAC complex is involved in an array of biological and cellular processes, including cell cycle progression, genomic stability, embryonic development, and homeostasis. Abnormal recruitment of this complex or alteration of its enzymatic activity has been implicated in neoplastic transformation.
Topics: Autophagy-Related Proteins; Carrier Proteins; Genes, Fungal; Histone Deacetylase 2; Histone Deacetylases; Multiprotein Complexes; Protein Structure, Tertiary; RNA-Binding Proteins; Repressor Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 19505602
DOI: 10.1016/j.bbagrm.2009.05.007 -
Cellular and Molecular Life Sciences :... Nov 2008Despite the common occurrence of forkhead associated (FHA) phosphopeptide-binding domains and really interesting new gene (RING) E3 ubiquitin ligase domains, gene... (Review)
Review
Despite the common occurrence of forkhead associated (FHA) phosphopeptide-binding domains and really interesting new gene (RING) E3 ubiquitin ligase domains, gene products containing both an N-terminal FHA domain and C-terminal RING domain constitute a highly distinctive intersection. Characterized FHA-RING ligases include the two vertebrate proteins, Checkpoint with FHA and RING (Chfr) and RING finger 8 (Rnf8), as well as three fungal proteins, Defective in mitosis (Dma1), Chf1 and Chf2. These FHA-RING ligases play roles in negative regulation of the cell division cycle, apparently by coupling protein phosphorylation events to specific ubiquitylation of target proteins. Here, the available data on upstream and downstream regulation of and by FHA-RING ligases are reviewed.
Topics: ADAM Proteins; Cell Cycle; Cell Cycle Proteins; Cell Division; DNA Repair; DNA-Binding Proteins; Genes, cdc; Humans; Models, Biological; Neoplasm Proteins; Poly-ADP-Ribose Binding Proteins; Protein Interaction Mapping; Protein Processing, Post-Translational; Protein Structure, Tertiary; Saccharomyces cerevisiae Proteins; Schizosaccharomyces; Schizosaccharomyces pombe Proteins; Sequence Alignment; Structure-Activity Relationship; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 18597043
DOI: 10.1007/s00018-008-8220-1 -
Biochimica Et Biophysica Acta Jan 2012The recognition of the conserved ATP-binding domains of Pex1p, p97 and NSF led to the discovery of the family of AAA-type ATPases. The biogenesis of peroxisomes... (Review)
Review
The recognition of the conserved ATP-binding domains of Pex1p, p97 and NSF led to the discovery of the family of AAA-type ATPases. The biogenesis of peroxisomes critically depends on the function of two AAA-type ATPases, namely Pex1p and Pex6p, which provide the energy for import of peroxisomal matrix proteins. Peroxisomal matrix proteins are synthesized on free ribosomes in the cytosol and guided to the peroxisomal membrane by specific soluble receptors. At the membrane, the cargo-loaded receptors bind to a docking complex and the receptor-docking complex assembly is thought to form a dynamic pore which enables the transition of the cargo into the organellar lumen. The import cycle is completed by ubiquitination- and ATP-dependent dislocation of the receptor from the membrane to the cytosol, which is performed by the AAA-peroxins. Receptor ubiquitination and dislocation are the only energy-dependent steps in peroxisomal protein import. The export-driven import model suggests that the AAA-peroxins might function as motor proteins in peroxisomal import by coupling ATP-dependent removal of the peroxisomal import receptor and cargo translocation into the organelle.
Topics: ATPases Associated with Diverse Cellular Activities; Adenosine Triphosphatases; Cell Cycle Proteins; Endoplasmic Reticulum-Associated Degradation; Membrane Proteins; Peroxisomes; Protein Multimerization; Protein Structure, Tertiary; Protein Transport; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Valosin Containing Protein
PubMed: 21963882
DOI: 10.1016/j.bbamcr.2011.09.005