Crystal Structure of Na ⁺ , K ⁺ -ATPase in the Na ⁺ -Bound State

Abstract

site IIIa is associated with Na + release. High-resolution structures that accurately reveal Na + coordination and associated hydrogen-bonding networks will be essential for a better understanding of the structure-function relations of ion exchange , transport, and specificity and how the mechanism is affected by regulation and disease-related mutations. ence,

Uncovering Neurodegenerative Protein Modifications via Proteomic Profiling

“…The α-subunit consists of four domains: N (nucleotide binding), A (actuator), P (phosphorylation), and M (membrane) domains. The major conformational changes during E1P to E2P transition are the 35°rotation of P domain, the rotation of N domain away from the P domain, and the rotation and translation of A domain that relocates the TGE sequence near to the catalytic site (Kuhlbrandt, 2004;Nyblom et al, 2013;Shinoda et al, 2009). previously shown that mutation of Asn 715 to Ala can decrease the affinity of Na + /K + -ATPase for Mg 2+ ions (Pedersen, Jorgensen, & Jorgensen, 2000). Structural modeling experiments showed that the three deamidated residues present in VaD samples were located near to the catalytic site of this protein.…”

Mechanistic principles of ion transport in the Na,K-ATPase

“…In the following years the structure was published with increased resolution [70], and subsequently further conformations became available with atomic resolution, E 2 conformations with ouabain and other cardiac steroid-bound structures [71][72][73], as well as an E 1 conformation with 3 Na + bound [74,75]. The latter structures support strongly the concept that the K + binding site and two of the Na + binding sites are formed by the same moieties of the membrane domain of the α subunit between transmembrane helices TM4, TM5 and TM6.…”

“…The third Na + -binding site is a highly specific site that doesn't allow binding of other cations. Its location is assumed to be close to TM5, but slightly different in both published structures, either between TM5, TM6, TM8 [75] or between TM5, TM7, TM8 [74]. In both cases, however, the long TM5 helix that connects the membrane domain with the P domain is participating (and affected) by binding of the third Na + .…”

P2C-Type ATPases and Their Regulation

“…It has been reported that Na + /K + -ATPase and SERCA sequence structures are 30 % identical and 65 % similar [2], this is the reason why SERCA model was used for Na + /K + -ATPase studies until it was crystalized. Also, both proteins have an α subunit, with 10 transmembrane spans, but Na + /K + -ATPase differs in having also β and γ isoforms, with 12 transmembrane spans, so two subunits should affect the α subunit conformation of Na + /K + -ATPase [3,4]. In this review, we concentrate only in P2C-ATPases: H + /K + -ATPases and Na + /K + -ATPase.…”

“…Na + /K + -ATPase uses almost 30 % of the ATP available to the cell and has important roles that include the following: (1) maintaining ionic balance, (2) providing energy through the coupled transport of nutrients, (3) re-establishing the ionic gradient after an action potential in neurons, (4) helping to maintain a gradient in epithelial cells, and (5) activating lymphocytes [9].…”