1. Volume 26, Issue 1, Pages 20-27.e3 (January 2018)
High-Resolution Cryoelectron Microscopy Structure of the Cyclic Nucleotide-Modulated Potassium Channel MloK1 in a Lipid Bilayer 
Julia Kowal, Nikhil Biyani, Mohamed Chami, Sebastian Scherer, Andrzej J. Rzepiela, Paul Baumgartner, Vikrant Upadhyay, Crina M. Nimigean, Henning Stahlberg 
Structure 
Volume 26, Issue 1, Pages e3 (January 2018)
DOI: /j.str
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2. Structure 2018 26, 20-27.e3DOI: (10.1016/j.str.2017.11.012)
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3. Figure 1 Cryo-EM Map of MloK1 Channel Tetramer with cAMP
(A) Extracellular top view of one tetramer. The structure of individual monomers shown in different colors in cryo-EM density (gray). The voltage sensor domains and the CNBDs wrap around the adjacent subunit pore domain. CNBDs are in fainter shades as they are located below the transmembrane domains. The current atomic model (PDB: 6EO1) is fitted into the density.
(B) Side view of the channel. Dashed lines indicate the membrane level.
(C) Cross-section through middle of the channel shown in (B). Main channel sections are indicated on the figure.
(D) Simple topology cartoon of MloK1 protomer, viewed parallel to the membrane. Different regions (S1–S6, pore loop, extracellular loops, selectivity filter, C-linker, CNBD) of the channel are illustrated in different colors.
All scale bars, 2 nm.
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4. Figure 2 Structural Details of Different MloK1 Channel Features
(A) Long inner pore helix composed of helix S6 continued with the C-linker.
(B) Densities between helices S3 and S4, labeled.
(C) Cross-section through the cyclic nucleotide-binding domain. β sheets are indicated; helices and both termini of MloK1 are labeled as N and C. MloK1 domains are colored as in Figure 1D.
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5. Figure 3 Helix Bundle Crossing and Selectivity Filter
(A) Overview of the superimposed X-ray structure of transmembrane region of MloK1 (PDB: 3BEH; Clayton et al., 2008, yellow ribbons and purple ions) and current (PDB: 6EO1, blue) model. Three areas are highlighted: S6 helix-bundle crossing, turret formed by the S5 helix and part of the P loop, S4-S5 linker.
(B) Intracellular view of a cross-section through middle of the pore shown in (A), with the X-ray structure in yellow and the current model in blue.
(C) At the level of the helix bundle crossing (A207), MloK1's pore is about twice the diameter of that of the X-ray structure of MloK1 (5.6 versus 10.6 Å).
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6. Figure 4 MloK1 Siphon and C-Linker Structures
Cross-section through the middle of the MloK1 tetramer showing just two opposing subunits. The “siphon” loop formed by the turns directly connects the long inner helix (S6 and C-linker) to the CNBD. Parts of the structure were colored as on the topology in Figure 1D; the siphon is labeled. Electron density is gray.
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7. Figure 5 Interactions between Transmembrane Domains and CNBDs
(A) Overview of MloK1 CNBD's inter- and intra-subunit interactions.
(B) The CNBD of one subunit (blue) is within contact distance with the S2-S3 loop of the adjacent subunit (red).
(C) The N-terminal amino acid chain (before helix S1, residues 1–15, labeled) lies on top and on the inner side of the CNBD of the same subunit (blue). The N terminus is rich in hydrophobic amino acids (Val, Leu, Pro, Phe, Leu, and Ile). Approximate residue locations are indicated, but they were not resolved in the map.
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8. Figure 6 Cartoon Illustrating a Proposed Gating Model in MloK1
(A) When cAMP is bound, the “siphons” (red) are bent and the CNBDs (yellow) interact with the S2-S3 loop of the voltage sensor of the adjacent subunit, while being in direct contact with the N terminus of its own subunit, as shown in the current structure.
(B) We propose that in the absence of cAMP, a CNBD conformational change leads to a change in the siphons bringing the CNBDs in a conformation more distant from the membrane plane with a motion suggested by the arrows. Transmembrane domains are in navy, membrane in light green.
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