Structural Characterization of the Boca/Mesd Maturation Factors for LDL-Receptor-Type beta Propeller Domains
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 {beta} 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 {beta} 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.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Organization:
- USDOE SC OFFICE OF SCIENCE (SC)
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1042095
- Report Number(s):
- BNL-97773-2012-JA; TRN: US201212%%506
- Journal Information:
- Structure, Vol. 19, Issue 3; ISSN 0969-2126
- Country of Publication:
- United States
- Language:
- English
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