Transmembrane Heme Delivery Systems

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1998 Jun 6

PMID 9560218

Citations 42

Authors

B S Goldman

D L Beck

E M Monika

R G Kranz

Affiliations

Soon will be listed here.

Abstract

Heme proteins play pivotal roles in a wealth of biological processes. Despite this, the molecular mechanisms by which heme traverses bilayer membranes for use in biosynthetic reactions are unknown. The biosynthesis of c-type cytochromes requires that heme is transported to the bacterial periplasm or mitochondrial intermembrane space where it is covalently ligated to two reduced cysteinyl residues of the apocytochrome. Results herein suggest that a family of integral membrane proteins in prokaryotes, protozoans, and plants act as transmembrane heme delivery systems for the biogenesis of c-type cytochromes. The complete topology of a representative from each of the three subfamilies was experimentally determined. Key histidinyl residues and a conserved tryptophan-rich region (designated the WWD domain) are positioned at the site of cytochrome c assembly for all three subfamilies. These histidinyl residues were shown to be essential for function in one of the subfamilies, an ABC transporter encoded by helABCD. We believe that a directed heme delivery pathway is vital for the synthesis of cytochromes c, whereby heme iron is protected from oxidation via ligation to histidinyl residues within the delivery proteins.

Citing Articles

Structural basis of membrane machines that traffick and attach heme to cytochromes.

Huynh J, Lowder E, Kranz R J Biol Chem. 2023; 299(11):105332.

PMID: 37827288 PMC: 10663686. DOI: 10.1016/j.jbc.2023.105332.

Structure-Function Analysis of the Bifunctional CcsBA Heme Exporter and Cytochrome Synthetase.

Sutherland M, Tran N, Tillman D, Jarodsky J, Yuan J, Kranz R mBio. 2018; 9(6).

PMID: 30563894 PMC: 6299221. DOI: 10.1128/mBio.02134-18.

The CcmC-CcmE interaction during cytochrome maturation by System I is driven by protein-protein and not protein-heme contacts.

Shevket S, Gonzalez D, Cartwright J, Kleanthous C, Ferguson S, Redfield C J Biol Chem. 2018; 293(43):16778-16790.

PMID: 30206118 PMC: 6204919. DOI: 10.1074/jbc.RA118.005024.

Structurally Mapping Endogenous Heme in the CcmCDE Membrane Complex for Cytochrome c Biogenesis.

Sutherland M, Jarodsky J, Ovchinnikov S, Baker D, Kranz R J Mol Biol. 2018; 430(8):1065-1080.

PMID: 29518410 PMC: 5889519. DOI: 10.1016/j.jmb.2018.01.022.

Regulation of intracellular heme trafficking revealed by subcellular reporters.

Yuan X, Rietzschel N, Kwon H, Walter Nuno A, Hanna D, Phillips J Proc Natl Acad Sci U S A. 2016; 113(35):E5144-52.

PMID: 27528661 PMC: 5024633. DOI: 10.1073/pnas.1609865113.

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