Title: Transmembrane helix 11 is a genuine regulator of the endoplasmic reticulum Ca2+ pump and acts as a functional parallel of β-subunit on α-Na+,K+-ATPase
Authors: Gorski, Przemek A
Trieber, Catharine A
Larivière, Els
Schuermans, Marleen
Wuytack, Frank
Young, Howard S
Vangheluwe, Peter # ×
Issue Date: Jun-2012
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:287 issue:24 pages:19876-19885
Abstract: The housekeeping sarco(endo)plasmic reticulum Ca(2+) ATPase SERCA2b transports Ca(2+) across the endoplasmic reticulum membrane maintaining a vital Ca(2+) gradient. Compared with the muscle-specific isoforms SERCA2a and SERCA1a, SERCA2b houses an 11th transmembrane segment (TM11) and a short luminal extension (LE) at its C terminus (2b-tail). The 2b-tail imposes a 2-fold higher apparent Ca(2+) affinity and lower V(max). Previously, we assumed that LE is the sole functional region of the 2b-tail and that TM11 is a passive element providing an additional membrane passage. However, here we show that peptides corresponding to the TM11 region specifically modulate the activity of the homologous SERCA1a in co-reconstituted proteoliposomes and mimic the 2b-tail effect (i.e. lower V(max) and higher Ca(2+) affinity). Using truncated 2b-tail variants we document that TM11 regulates SERCA1a independently from LE, confirming that TM11 is a second, previously unrecognized functional region of the 2b-tail. A phylogenetic analysis further indicates that TM11 is the oldest and most conserved feature of the 2b-tail, found in the SERCA pump of all Bilateria, whereas LE is only present in Nematoda and vertebrates. Considering remarkable similarities with the Na(+),K(+)-ATPase α-β interaction, we now propose a model for interaction of TM11 with TM7 and TM10 in the anchoring subdomain of the Ca(2+) pump. This model involves a TM11-induced helix bending of TM7. In conclusion, more than just a passive structural feature, TM11 acts as a genuine regulator of Ca(2+) transport through interaction with the pump.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Cellular Transport Systems
Biomedical Sciences Teaching Methodology and Practicals
× corresponding author
# (joint) last author

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