Structural and energetic analysis of metastable intermediate states in the E1P–E2P transition of Ca <sup>2+</sup> -ATPase
Chigusa Kobayashi, Yasuhiro Matsunaga, Jaewoon Jung, Yuji Sugita
Abstract
Significance Ion pumps (or P-type ATPases) are membrane proteins, which transport ions through biological membranes against a concentration gradient, a function essential for many biological processes, such as muscle contraction, neurotransmission, and metabolism. Molecular mechanisms underlying active ion transport by ion pumps have been investigated by biochemical experiments and high-resolution structure analyses. Here, the transition of sarcoplasmic reticulum Ca 2+ -ATPase upon dissociation of Ca 2+ is investigated using atomistic molecular dynamics simulations. We find intermediate structures along the pathway are stabilized by transient interactions between A- and P-domains as well as lipid molecules in the transmembrane helices.