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Related Experiment Videos

Transmembrane heme delivery systems

B S Goldman1, D L Beck, E M Monika

  • 1Department of Biology, Washington University, One Brookings Drive, St. Louis, MO 63130, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 6, 1998
PubMed
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Integral membrane proteins transport heme across membranes for cytochrome c synthesis. Key residues and a WWD domain are crucial for this heme delivery pathway, protecting iron from oxidation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Heme proteins are essential for numerous biological processes.
  • The mechanism of heme transport across membranes for biosynthesis remains largely unknown.
  • Cytochrome c biosynthesis requires heme delivery to the periplasm or intermembrane space for ligation.

Purpose of the Study:

  • To elucidate the molecular mechanisms of transmembrane heme transport.
  • To identify proteins involved in heme delivery for c-type cytochrome biogenesis.
  • To characterize the structure and function of these heme delivery systems.

Main Methods:

  • Experimental determination of the complete topology of representative integral membrane proteins from three subfamilies.
  • Identification of key histidinyl residues and a conserved tryptophan-rich region (WWD domain).

Related Experiment Videos

  • Functional analysis of histidinyl residues in an ABC transporter (helABCD).
  • Main Results:

    • A family of integral membrane proteins in prokaryotes, protozoans, and plants functions as transmembrane heme delivery systems.
    • Key histidinyl residues and the WWD domain are conserved and positioned at the cytochrome c assembly site.
    • Essentiality of histidinyl residues for function was demonstrated in the helABCD ABC transporter.

    Conclusions:

    • Integral membrane proteins facilitate directed heme delivery for c-type cytochrome biogenesis.
    • The heme delivery pathway likely protects heme iron from oxidation through ligation to histidinyl residues within the transport proteins.
    • This pathway is vital for the synthesis of functional cytochromes c across diverse organisms.