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Phospholamban binds in a compact and ordered conformation to the Ca-ATPase
Jinhui Li1, Yijia Xiong, Diana J Bigelow
1Cell Biology Group, Department of Biological Sciences, Fundamental Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
Biochemistry
|January 14, 2004
Summary
Phospholamban (PLB) adopts a disordered structure alone but a highly ordered conformation when bound to the Ca-ATPase. This binding induces a reorientation of the Ca-ATPase, explaining PLB
Area of Science:
- Biochemistry
- Structural Biology
- Cardiovascular Physiology
Background:
- Phospholamban (PLB) regulates the cardiac Ca-ATPase pump.
- Previous models suggested PLB adopts an extended conformation when bound to Ca-ATPase.
Purpose of the Study:
- To directly measure the conformation of PLB in the presence and absence of Ca-ATPase.
- To test existing models of the PLB-Ca-ATPase complex.
Main Methods:
- Fluorescence resonance energy transfer (FRET) was used to measure distances between PLB domains.
- PLB was reconstituted into proteoliposomes with or without Ca-ATPase.
Main Results:
- Unbound PLB exhibits conformational heterogeneity with a broad distribution of distances.
- Bound PLB adopts a unique, highly ordered conformation with a significantly reduced distance between domains.
- The observed conformation contradicts models predicting an extended PLB structure.
Conclusions:
- PLB binding induces a unique, compact conformation, challenging current models.
- PLB binding likely causes a reorientation of the Ca-ATPase nucleotide binding domain.
- This conformational change in Ca-ATPase underlies PLB's inhibitory effect on calcium sensitivity.