Motion in Calcium ATPase (rabbit sarcoplasmic reticulum [capump]

[ jump to morphs ]

Classification Suspected Fragment Motion, Shear Mechanism [F-s-2]

Structures 1SU4 Conformation 1 1T5S Conformation 2 1T5T Conformation 3 1WPG Conformation 4 1IW0 Conformation 5

Description The structures of the Ca2+-ATPase have been determined for five different states by X-ray crystallography. Detailed comparison of the structures in the Ca2+ bound form and unbound form reveals that very large rearrangements of the transmembrane helices take place accompanying Ca2+ dissociation and binding and that they are mechanically linked with equally large movements of the cytoplasmic domains. The meanings of the rearrangements of the transmembrane helices and those of the cytoplasmic domains as well as the mechanistic roles are becoming clearer. Furthermore, the roles of critical amino acid residues identified by extensive mutagensis studies are becoming evident in terms of atomic structure. Description by Dr. William Rice (Stokes lab, NYU med school): "Ca-ATPase transports cytoplasmic Ca into the lumen of the SR/ER (or outside of the cell in the case of plasma membrane Ca-ATPase), using the energy of ATP to pump against the gradient. In the simplified cycle, binding of cytoplasmic Ca induces the enzyme to go from E2 to E1-Ca. In this state, there are 2 Ca ions bound to high affinity sites in the membrane domain. The Ca ions are facing the cytoplasm in this state. The binding of Ca in the membrane is communicated to the cytoplasmic domain: the enzyme can be phosphorylated by ATP only after Ca has been bound. It is this tight coupling between cytoplasmic and membrane-spanning regions that allows the molecule to work as a pump. It is then phosphorylated by ATP, forming E1~P. In this state, Ca is occluded within the membrane. E1~P then rearranges to E2-P, and the Ca-binding sites rearrange: their affinity lowers ~1000 fold, and they face the lumen of the ER/SR. Ca dissociates into the lumen, the phosphoenzyme bond is hydrolysed and the pump goes back to the E2 state.

Particular values describing motion Creation Date = 20050815 Experimental Methods = xc (X-ray crystallography and CryoEM) Modification Date = 2005-08-15 13:06:58.000

References C Toyoshima, M Nakasako, H Nomura, H Ogawa (2000). Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6A resolution. Nature. 405: 647-655. [Medline info for 10864315] Xu C, Rice WJ, He W, Stokes DL. A structural model for the catalytic cycle of Ca(2+)-ATPase. J Mol Biol. 2002 Feb 8316(1):201-11. [Medline info for 11829513] C Toyoshima, T Mizutani (2004). Crystal structure of the calcium pump with a bound ATP analogue. Nature. 430: 529-535. [Medline info for 15229613] C Toyoshima, H Nomura (2002). Structural changes in the calcium pump accompanying the disocciation of calcium. Nature. 418: 605-611. [Medline info for 12167852] C Toyoshima, H Nomura, T Tsuda (2004). Lumenal gating mechanism revealed in calcium pump crystal structures with phosphate analogues. Nature. 432: 286-286 [Medline info for 15448704] TL Sorensen, JV Moller, P Nissen (2004). Phosphoryl transfer and calcium ion occlusion in the calcium pump. Science. 304: 1672-1675. [Medline info for 15192230] C Olesen, TL Sorensen, RC Nielsen, JV Moller, P Nissen (2004). Dephosphorylation of the calcium pump coupled to counterion occlusion. Science. 306: 2251-2255. [Medline info for 15618517]

GO terms associated with structures Molecular function catalytic activity, hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances, calcium-transporting ATPase activity, ATPase activity, coupled to transmembrane movement of ions, phosphorylative mechanism, ATP binding, heme oxygenase (decyclizing) activity Cellular component integral to membrane, membrane Biological process calcium ion transport, metabolism, proton transport, cation transport, heme oxidation

Morphs

[ show all images ]

Best representative Morph Morph name Structure #1 Structure #2 Residues [ ] [ ] [ ] [ ]

---

Copyright 1995-2005 M. Gerstein, W. Krebs, S. Flores, N. Echols, and others
Email: Mark.Gerstein _at_ yale.edu