4KYT

The structure of superinhibitory phospholamban bound to the calcium pump SERCA1a

Summary for 4KYT

• Entry DOI: 10.2210/pdb4kyt/pdb
• Related PRD ID: PRD_900001
• Descriptor: SERCA1a, Cardiac phospholamban, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: transmembrane helices, calcium pump, p-type atpase, membrane, membrane protein
• Biological source: Canis lupus familiaris (dogs); More
• Total number of polymer chains: 3
• Total formula weight: 122220.93

Authors

Hurley, T.D.,Akin, B.L.,Jones, L.R. (deposition date: 2013-05-29, release date: 2013-09-04, Last modification date: 2024-10-09)

Primary citation

Akin, B.L.,Hurley, T.D.,Chen, Z.,Jones, L.R.
The structural basis for phospholamban inhibition of the calcium pump in sarcoplasmic reticulum.
J.Biol.Chem., 288:30181-30191, 2013

PubMed Abstract: P-type ATPases are a large family of enzymes that actively transport ions across biological membranes by interconverting between high (E1) and low (E2) ion-affinity states; these transmembrane transporters carry out critical processes in nearly all forms of life. In striated muscle, the archetype P-type ATPase, SERCA (sarco(endo)plasmic reticulum Ca(2+)-ATPase), pumps contractile-dependent Ca(2+) ions into the lumen of sarcoplasmic reticulum, which initiates myocyte relaxation and refills the sarcoplasmic reticulum in preparation for the next contraction. In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. cAMP-dependent phosphorylation of PLB reverses Ca(2+)-ATPase inhibition with powerful contractile effects. Here we present the long sought crystal structure of the PLB-SERCA complex at 2.8-Å resolution. The structure was solved in the absence of Ca(2+) in a novel detergent system employing alkyl mannosides. The structure shows PLB bound to a previously undescribed conformation of SERCA in which the Ca(2+) binding sites are collapsed and devoid of divalent cations (E2-PLB). This new structure represents one of the key unsolved conformational states of SERCA and provides a structural explanation for how dephosphorylated PLB decreases Ca(2+) affinity and depresses cardiac contractility.

PubMed: 23996003
DOI: 10.1074/jbc.M113.501585

Experimental method

X-RAY DIFFRACTION (2.833 Å)