Structural insights into the MMACHC-MMADHC protein complex involved in vitamin B12 trafficking

DOI: 10.1074/jbc.M115.683268
PMID: 26483544

Authors: Sean Froese (University Children’s Hospital, Zurich) , Jolanta Kopec (University of Oxford) , Fiona Fitzpatrick (University of Oxford) , Marion Schuller (Nuffield Department of Clinical Medicine) , Thomas Mccorvie (University of Oxford) , Rod Chalk (Nuffield Department of Clinical Medicine) , Tanja Plessl (University Children’s Hospital) , Victoria Fettelschoss (University Children’s Hospital) , Brian Fowler (University Children’s Hospital) , Matthias R. Baumgartner (University Children’s Hospital) , Wyatt Yue (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry

State: Published (Approved)
Published: October 2015
Diamond Proposal Number(s): 10619

Abstract: Background: Two intracellular proteins, MMACHC and MMADHC, functionally interact for cobalamin trafficking. Results: MMADHC crystal structure reveals protein-interacting regions and unexpected homology to MMACHC; mutations on either protein interfere with complex formation via different mechanisms. Conclusion: Complex formation likely depends on prior cobalamin processing and can be broken by disease mutations. Significance: MMACHC-MMADHC heterodimerization forms the essential trafficking chaperone delivering cobalamin to client enzymes.

Journal Keywords: Nitroreductase Fold; Protein-Protein Interaction; Small Angle X-Ray Scattering (Saxs); Vitamin B12; Crystal Structure; Site-Directed Mutagenesis; Metabolic Disease

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS , I04-Macromolecular Crystallography

Added On: 24/10/2015 14:06

Documents:
PIIS0021925820395351.pdf

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)