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Calcium binding to the transmembrane domain of the sarcoplasmic reticulum Ca 2+ ‐ATPase: Insights from molecular modeling
Author(s) -
Costa Valeria,
Carloni Paolo
Publication year - 2002
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10219
Subject(s) - endoplasmic reticulum , chemistry , transmembrane protein , biophysics , transmembrane domain , calcium , molecular dynamics , calcium binding protein , atpase , crystallography , ion , calcium atpase , protein structure , lipid bilayer , membrane , biochemistry , biology , computational chemistry , enzyme , receptor , organic chemistry
Sarcoplasmic reticulum Ca 2+ ‐ ATPase pumps Ca 2+ ions from muscle cells to the sarcoplasmic reticulum. Here we use molecular dynamics and electrostatic modeling to investigate structural and dynamical features of key intermediates in the Ca 2+ binding process of the protein. Structural models of the protein (containing either two, one, or no calcium ions in the transmembrane domain) are constructed based on the X‐ray structure by Toyoshima et al. (Nature 2000;405:647–655). The protein is embedded in a water/octane bilayer, which mimics the water/membrane environment. Our calculations provide information on the hydration of the two Ca 2+ ions, not emerging from the X‐ray structure. Furthermore, they indicate that uptake of the metal ions causes large structural rearrangements of the metal binding sites. In addition, they suggest that the two ions reach their binding sites via two specific pathways. Finally, they allow identification of residues in the outer mouth of the protein that might interact with the Ca 2+ ions during the binding process. Proteins 2003;50:104–113. © 2002 Wiley‐Liss, Inc.