Crystal Structure of the VHS and FYVE Tandem Domains of Hrs, a Protein Involved in Membrane Trafficking and Signal Transduction

Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA.
Cell (Impact Factor: 32.24). 03/2000; 100(4):447-56. DOI: 10.1016/S0092-8674(00)80680-7
Source: PubMed


We have determined the 2 A X-ray structure of the 219-residue N-terminal VHS and FYVE tandem domain unit of Drosophila Hrs. The unit assumes a pyramidal structure in which the much larger VHS domain (residues 1-153) forms a rectangular base and the FYVE domain occupies the apical end. The VHS domain is comprised of an unusual "superhelix" of eight alpha helices, and the FYVE domain is mainly built of loops, two double-stranded antiparallel sheets, and a helix stabilized by two tetrahedrally coordinated zinc atoms. The two-domain structure forms an exact 2-fold-related homodimer through antiparallel association of mainly FYVE domains. Dimerization creates two identical pockets designed for binding ligands with multiple negative charges such as citrate or phosphatidylinositol 3-phosphate.

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Available from: Thomas E Lloyd, Oct 01, 2015
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    • "The Vps - 27 , Hrs , and STAM ( VHS ) domain is structurally very similar to the ENTH domain , and the ENTH , ANTH , and VHS proteins are often treated as a superfamily ( Interpro IPR008942=ENTH / VHS ) . Similar to the ENTH domain , the VHS domain contains eight a - helices and is ; 150 amino acids in length ( Mao et al . , 2000 ) . Proteins with a VHS domain often have other functionally important structured domains and can be grouped accordingly ( for an overview , see Lohi et al . , 2002 ) . Members of one such group contain the Fab - 1 , YGL023 , Vps27 , and EEA1 ( FYVE ) domain , which is required for PtdIns ( 3 ) P binding at the animal early endosome ( E"
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    ABSTRACT: Coated vesicles provide a major mechanism for the transport of proteins through the endomembrane system of plants. Transport between the endoplasmic reticulum and the Golgi involves vesicles with COPI and COPII coats, whereas clathrin is the predominant coat in endocytosis and post-Golgi trafficking. Sorting of cargo, coat assembly, budding, and fission are all complex and tightly regulated processes that involve many proteins. The mechanisms and responsible factors are largely conserved in eukaryotes, and increasing organismal complexity tends to be associated with a greater numbers of individual family members. Among the key factors is the class of ENTH/ANTH/VHS domain-containing proteins, which link membrane subdomains, clathrin, and other adapter proteins involved in early steps of clathrin coated vesicle formation. More than 30 Arabidopsis thaliana proteins contain this domain, but their generally low sequence conservation has made functional classification difficult. Reports from the last two years have greatly expanded our knowledge of these proteins and suggest that ENTH/ANTH/VHS domain proteins are involved in various instances of clathrin-related endomembrane trafficking in plants. This review aims to summarize these new findings and discuss the broader context of clathrin-dependent plant vesicular transport. © 2014 American Society of Plant Biologists. All rights reserved.
    The Plant Cell 11/2014; DOI:10.1105/tpc.114.131680 · 9.34 Impact Factor
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    • "The ∝ − helices of the ENTH, ANTH and VHS domains were localized on the Multiple Alignment of Complete Sequences (MACS) based on the protein structures found in the PDB database. Structure of TOM is 1ELK [24], VHS is 1DVP [8], Epsin1 is 1INZ [55], GGA1 is 1JWF [25], CALM is 1HF8 [9] and STAM is 1X5B (by Tochio, N., Koshiba, S., Inoue, M., Kigawa, T. and Yokoyama, S. for the RIKEN Structural Genomics/Proteomics Initiative (RSGI)). "
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    ABSTRACT: Membrane trafficking involves the complex regulation of proteins and lipids intracellular localization and is required for metabolic uptake, cell growth and development. Different trafficking pathways passing through the endosomes are coordinated by the ENTH/ANTH/VHS adaptor protein superfamily. The endosomes are crucial for eukaryotes since the acquisition of the endomembrane system was a central process in eukaryogenesis. Our in silico analysis of this ENTH/ANTH/VHS superfamily, consisting of proteins gathered from 84 complete genomes representative of the different eukaryotic taxa, revealed that genomic distribution of this superfamily allows to discriminate Fungi and Metazoa from Plantae and Protists. Next, in a four way genome wide comparison, we showed that this discriminative feature is observed not only for other membrane trafficking effectors, but also for proteins involved in metabolism and in cytokinesis, suggesting that metabolism, cytokinesis and intracellular trafficking pathways co-evolved. Moreover, some of the proteins identified were implicated in multiple functions, in either trafficking and metabolism or trafficking and cytokinesis, suggesting that membrane trafficking is central to this co-evolution process. Our study suggests that membrane trafficking and compartmentalization were not only key features for the emergence of eukaryotic cells but also drove the separation of the eukaryotes in the different taxa.
    BMC Genomics 07/2012; 13(1):297. DOI:10.1186/1471-2164-13-297 · 3.99 Impact Factor
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    • "The ESCRT-0 complex consists of two subunits, Hrs (Vps27 in yeast) and STAM1/2 (Hse1 in yeast). Hrs contains a FYVE zinc finger domain which binds PtdIns(3)P providing membrane recruitment and endosomal specificity for the ESCRT-0 complex (Mao et al., 2000). Hrs and STAM1/2 bind ubiquitin via their UIM and VHS ubiquitin domains respectively, which are essential for efficient sorting of ubiquitinated proteins (Bishop et al., 2002; Mizuno et al., 2003; Bache et al., 2006). "
    Current Frontiers and Perspectives in Cell Biology, 04/2012; , ISBN: 978-953-51-0544-2
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