The Lumenal Loop Met672–Pro707 of Copper-transporting ATPase ATP7A Binds Metals and Facilitates Copper Release from the Intramembrane Sites

Abstract

The copper-transporting ATPase ATP7A has an essential role in human physiology. ATP7A transfers the copper cofactor to metalloenzymes within the secretory pathway; inactivation of ATP7A results in an untreatable neurodegenerative disorder, Menkes disease. Presently, the mechanism of ATP7A-mediated copper release into the secretory pathway is not understood. We demonstrate that the characteristic His/Met-rich segment

Periplasmic proteins encoded by VCA0261–0260 and VC2216 genes together with copA and cueR products are required for copper tolerance but not for virulence in Vibrio cholerae

“…in R. metallidurans copG lies downstream of the ATPase-encoding gene copF) (Monchy et al, 2006). In fact, one of the least studied aspects of the transport mechanism of Cu + -ATPases is how the ion is released from the intramembrane metal-binding site into the periplasm (Barry et al, 2011;Raimunda et al, 2011). However, copper might not be found free in the periplasm and periplasmic copper chaperones have been described by Kim et al (2010) and Robinson & Winge (2010).…”

Distinctive Features of Catalytic and Transport Mechanisms in Mammalian Sarco-endoplasmic Reticulum Ca2+ ATPase (SERCA) and Cu+ (ATP7A/B) ATPases

“…In fact, structural studies of Legionella pneumophila (CopA) copper ATPase (58) do not reveal obvious involvement of acidic chains in the release phase of copper transport. Other specific mechanisms may be involved in promoting copper release from intramembrane sites of the copper ATPase, such as revealed by experiments on the Met-672-Pro-707 lumenal loop (59).…”

Adaptor Protein-1 Complex Affects the Endocytic Trafficking and Function of Peptidylglycine α-Amidating Monooxygenase, a Luminal Cuproenzyme

“…For measurement, samples were transferred to acid-treated 15-ml conical tubes. Data were quantified using a 9-point calibration standard (Common Elements Mix 2 Multi-Element Aqueous Standard, VHG Labs) in 1% HNO 3 . For each sample, data were acquired in triplicate and averaged.…”

“…If the His/Met-rich luminal loop of Atp7a transfers copper directly to PAM-1, as suggested by biochemical studies (3,4), the two proteins must spend some time in the same subcellular compartment. We used co-immunoprecipitation to search for evidence of an interaction.…”