Research ArticleCELL BIOLOGY

Cryo-EM structure of the calcium homeostasis modulator 1 channel

See allHide authors and affiliations

Science Advances  17 Jul 2020:
Vol. 6, no. 29, eaba8161
DOI: 10.1126/sciadv.aba8161
  • Fig. 1 Overall architecture of the drCALHM1 channel.

    (A) Cartoon representation and (B) surface representation of the cryo-EM density map of the drCALHM1 channels within the plasma membrane. The eight protomers are colored differently, and the lipid molecules densities are colored orange. (C) Cartoon representation and (D) surface representation of the cryo-EM density map of the drCALHM1 channel viewed from the extracellular space. Eight N-helices are located in the middle of the pore. (E) Cartoon representation and (F) surface representation of the cryo-EM density map of the drCALHM1 channel viewed from the intracellular space.

  • Fig. 2 Assembly of the drCALHM1 channel.

    (A) Schematic illustration outlining the protein secondary structures. P84 is shown in the red sphere. Dashed lines indicate parts that were not modeled in the structure. (B) Detailed view of one protomer. The glycosylation site N139 is shown as a stick model. Two disulfide bonds are indicated. (C) Superimposition of one drCALHM1 protomer (red) onto the hCALHM2 protomer (gray). Transmembrane helix (TH) 1 and 4 of the hCALHM2 protomer are labeled. (D) Cartoon representation of the drCALHM1 octamer (red) and the hCALHM2 undecamer (gray) after superimposition of one protomer from each oligomer. The green and blue dashed circles represent the assembly of these two oligomers. (E) Zoomed-in view of the dimer illustration. The green and blue dashed arrows represent the assembly of the drCALHM1 octamer and the hCALHM2 undecamer, respectively. The terms 1-A and 1-B denote two drCALHM1 protomers, while 2-A and 2-B denote two hCALHM2 protomers. The red arrows denote the potential steric clashes between the structural units.

  • Fig. 3 Intersubunit interactions.

    (A) Overall illustration of the intersubunit interactions in TM regions. The two protomers are colored orange and cyan. The numbers denote the TM helices. (B) Interactions between the N-helix and TM1 helices. The dashed line represents the hydrogen bond. (C to E) Interactions between TM4 and ECL1, between TM4 and TM2, and between TM4 and ECL2 are shown. (F) Overall illustration of eight CH1 helices assembled together. (G) Interactions between two CH1 helices. (H) Lipid molecules involved in intersubunit interactions. The two protomers are colored yellow and cyan. Three lipid molecules are presented in brown. Each TM helix is labeled.

  • Fig. 4 Ion conduction pore.

    (A) The ion conduction pathway of drCALHM1. The pores with or without the side chains of the N-helix are represented in pale orange and dark orange, respectively. (B) The pore radius along the central axis. The orange line represents the pore with the N-helix side chains. Extracellular domain (ECD), transmembrane domain (TMD) and intracellular domain (ICD) are labeled. (C) Side cutaway view of the electrostatic surface potential distribution. The range of the electrostatic surface potential is shown from −10 kT/e (red) to +10 kT/e (blue). (D) Cartoon representation showing the inner face of the drCALHM1 octamer. The four protomers are shown with different colors. Residues K122, R171, R176, and R179, which form a unique positive charge belt inside the pore, are labeled in one protomer and shown as spheres.

Supplementary Materials

  • Supplementary Materials

    Cryo-EM structure of the calcium homeostasis modulator 1 channel

    Yue Ren, Tianlei Wen, Zhiqin Xi, Shunjin Li, Jing Lu, Xing Zhang, Xue Yang, Yuequan Shen

    Download Supplement

    This PDF file includes:

    • Figs. S1 to S7
    • Table S1

    Files in this Data Supplement:

Stay Connected to Science Advances

Navigate This Article