Role of the extracellular domain of ABCG2 in porphyrin homeostasis
type: Distribution
access URL: https://theses.hal.science/tel-00868903
format: HTML
issued: 2026-05-09T12:31:29.619886
modified: 2026-05-09T12:31:29.600911

test_moissonnage_selune
type: Agent

Role of the extracellular domain of ABCG2 in porphyrin homeostasis
type: Dataset
contact point: Organization
  fn: CCSD
keyword: theses
keyword: porphyrines
keyword: porphyrins
keyword: interaction-proteine-ligand
keyword: infoeu-reposemanticsdoctoralthesis
keyword: detoxification
keyword: albumine
keyword: transporteur-abc
keyword: detoxication
keyword: proteinligand-interactions
keyword: atp-binding-cassette-transporters
keyword: atp-binding-cassette-sub-family-g-member-2-abcg2
keyword: sdvsalife-sciences-q-bioagricultural-sciences
keyword: albumin
landing page: https://theses.hal.science/tel-00868903
description: ABCG2 belongs to the ABC-transporter family, involved in drug resistance developed by cells, notably cancer cells. This transporter has also a physiological role of endobiotic detoxification, in particular porphyrins that are essential but potentially toxic molecules. This toxicity implies a specific handle, to avoid them to remain free in solution. In that context, we hypothesized that ABCG2 participate to this detoxification, limiting the intracellular porphyrin accumulation by presenting them to an extracellular partner. We show that ABCG2 transports heme and some of its derivatives and precursors. Interestingly, these porphyrins, unlike other ABCG2 (non-porphyric) substrates, can bind to an extracellular domain, specific of ABCG2, ECL3, 70 residues-long. ECL3 displays affinities for porphyrins in the range of 0.5 to 3.5 μM, high enough to allow their binding after transport. We also show that human serum albumin, implicated in heme detoxification, releases porphyrins bound to ECL3 by a direct interaction with ABCG2. This work established a better comprehension of ABCG2 role in porphyrin and in particular heme homeostasis regulation. In addition, our results contribute to elucidate part of the molecular mechanism by which such regulation is carried out.
identifier: NNT: 2010LYO10236
issued: 2026-05-09T12:31:29.615763
language: fr
modified: 2026-05-09T12:31:29.615768