論文 - 詳細
| RRC ID | 46541 |
|---|---|
| 著者 | Yuan X, Protchenko O, Philpott CC, Hamza I. |
| タイトル | Topologically conserved residues direct heme transport in HRG-1-related proteins. |
| ジャーナル | J Biol Chem |
| Abstract |
Caenorhabditis elegans and human HRG-1-related proteins are conserved, membrane-bound permeases that bind and translocate heme in metazoan cells via a currently uncharacterized mechanism. Here, we show that cellular import of heme by HRG-1-related proteins from worms and humans requires strategically located amino acids that are topologically conserved across species. We exploit a heme synthesis-defective Saccharomyces cerevisiae mutant to model the heme auxotrophy of C. elegans and demonstrate that, under heme-deplete conditions, the endosomal CeHRG-1 requires both a specific histidine in the predicted second transmembrane domain (TMD2) and the FARKY motif in the C terminus tail for heme transport. By contrast, the plasma membrane CeHRG-4 transports heme by utilizing a histidine in the exoplasmic (E2) loop and the FARKY motif. Optimal activity under heme-limiting conditions, however, requires histidine in the E2 loop of CeHRG-1 and tyrosine in TMD2 of CeHRG-4. An analogous system exists in humans, because mutation of the synonymous histidine in TMD2 of hHRG-1 eliminates heme transport activity, implying an evolutionary conserved heme transport mechanism that predates vertebrate origins. Our results support a model in which heme is translocated across membranes facilitated by conserved amino acids positioned on the exoplasmic, cytoplasmic, and transmembrane regions of HRG-1-related proteins. These findings may provide a framework for understanding the structural basis of heme transport in eukaryotes and human parasites, which rely on host heme for survival. |
| 巻・号 | 287(7) |
| ページ | 4914-24 |
| 公開日 | 2012-2-10 |
| DOI | 10.1074/jbc.M111.326785 |
| PII | S0021-9258(20)48145-1 |
| PMID | 22174408 |
| PMC | PMC3281596 |
| MeSH | Amino Acid Motifs Animals Biological Transport, Active / physiology Caenorhabditis elegans / chemistry Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / chemistry Carrier Proteins / genetics Carrier Proteins / metabolism* Heme / metabolism* Hemeproteins / chemistry Hemeproteins / genetics Hemeproteins / metabolism* Humans Models, Biological* Mutation Protein Structure, Tertiary Saccharomyces cerevisiae / chemistry Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae / metabolism |
| IF | 4.238 |
| 引用数 | 33 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm3199 tm2994 |