Efficient Purification and Reconstitution of ATP Binding Cassette Transporter B6 (ABCB6) for Functional and Structural Studies

Abstract

Background:The ABCB6 protein is proposed to transport coproporphyrinogen from the cytoplasm into the mitochondria. Results: Purified ABCB6 reconstituted into liposomes demonstrates coproporphyrinogen-stimulated ATP hydrolysis and coproporphyrinogen transport. Conclusion: ABCB6 does not require additional components for substrate-stimulated ATPase activity and substrate transport. Significance: Development of an in vitro system with pure and active ABCB6 for structure and functional studies is indicated.

A heme-binding domain controls regulation of ATP-dependent potassium channels

“…Hence, this particular mode of heme binding is specific to SUR2A and does not occur in other members of this family of ABC transporters. There is evidence for heme binding to ABC-transporter proteins (31)(32)(33)(34)(35) in other (unrelated) heme transport systems, but the heme-binding sites are not established.…”

TMEM14C is required for erythroid mitochondrial heme metabolism

“…ABCB6 (EC3.6.3), a mitochondrial outer membrane protein, has been implicated as a putative mitochondrial importer of CPgenIII, enabling the conversion of CPgenIII to PPgenIX by inner membrane-bound CPOX in the intermembrane space (51)(52)(53)(54); although, more recent work suggests that it is dispensable for heme synthesis and specifies the blood group Langereis (55). Based on the colocalization of TMEM14C and CPOX, and the restricted role of TMEM14C in mitochondrial heme synthesis, we propose that TMEM14C directly accepts PPgenIX Chemical complementation assays.…”

Functional Coupling of ATP-binding Cassette Transporter Abcb6 to Cytochrome P450 Expression and Activity in Liver

“…1f). These results suggest that although Abcb6 is capable of transporting heme precursors into the mitochondria (18,27) and plays a role in regulating porphyrin synthesis in vitro (17,18,26), Abcb6 deficiency in vivo does not have a significant impact on basal hepatic porphyrin or heme levels. These findings are consistent with recent reports that demonstrate a lack of functional association between Abcb6 and basal porphyrin synthesis in erythroid cells in vivo (18).…”