Structural characterization of the Boca/Mesd maturation factors for LDL-receptor-type β propeller domains

Structure. 2011 Mar 9;19(3):324-36. doi: 10.1016/j.str.2010.11.017.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans
  • Crystallography, X-Ray
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Epidermal Growth Factor / chemistry
  • Epidermal Growth Factor / metabolism
  • Escherichia coli
  • Ferredoxins / chemistry
  • Ferredoxins / metabolism
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Magnetic Resonance Spectroscopy
  • Mice
  • Models, Molecular
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Folding*
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Transport
  • Receptors, LDL / chemistry
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*

Substances

  • Drosophila Proteins
  • Ferredoxins
  • MESD protein, mouse
  • Molecular Chaperones
  • Protein Isoforms
  • Receptors, LDL
  • Recombinant Proteins
  • boca protein, Drosophila
  • Epidermal Growth Factor

Associated data

  • PDB/3OFE
  • PDB/3OFF
  • PDB/3OFG
  • PDB/3OFH