Abstract
Folding and trafficking of low-density lipoprotein receptor (LDLR) family members, which play essential roles in development and homeostasis, are mediated by specific chaperones. The Boca/Mesd chaperone family specifically promotes folding and trafficking of the YWTD β propeller-EGF domain pair found in the ectodomain of all LDLR members. Limited proteolysis, NMR spectroscopy, analytical ultracentrifugation, and X-ray crystallography were used to define a conserved core composed of a structured domain that is preceded by a disordered N-terminal region. High-resolution structures of the ordered domain were determined for homologous proteins from three metazoans. Seven independent protomers reveal a novel ferrodoxin-like superfamily fold with two distinct β sheet topologies. A conserved hydrophobic surface forms a dimer interface in each crystal, but these differ substantially at the atomic level, indicative of nonspecific hydrophobic interactions that may play a role in the chaperone activity of the Boca/Mesd family.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Caenorhabditis elegans
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Crystallography, X-Ray
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Drosophila Proteins / chemistry
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster
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Epidermal Growth Factor / chemistry
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Epidermal Growth Factor / metabolism
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Escherichia coli
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Ferredoxins / chemistry
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Ferredoxins / metabolism
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Humans
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Hydrophobic and Hydrophilic Interactions
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Magnetic Resonance Spectroscopy
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Mice
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Models, Molecular
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Molecular Chaperones / chemistry
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism*
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Molecular Sequence Data
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Protein Binding
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Protein Folding*
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Protein Isoforms / chemistry
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Protein Isoforms / genetics
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Protein Isoforms / metabolism*
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Protein Transport
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Receptors, LDL / chemistry
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Receptors, LDL / genetics
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Receptors, LDL / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism*
Substances
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Drosophila Proteins
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Ferredoxins
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MESD protein, mouse
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Molecular Chaperones
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Protein Isoforms
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Receptors, LDL
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Recombinant Proteins
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boca protein, Drosophila
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Epidermal Growth Factor
Associated data
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PDB/3OFE
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PDB/3OFF
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PDB/3OFG
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PDB/3OFH