9JJE
Nematostella vectensis TRPM2 tetramer in complex with ADPRP/Ca2+
Summary for 9JJE
| Entry DOI | 10.2210/pdb9jje/pdb |
| EMDB information | 61524 |
| Descriptor | Transient receptor potential cation channel subfamily M member-like 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | nematostella vectensis, trpm2, adprp, ca2+, membrane protein |
| Biological source | Nematostella vectensis (starlet sea anemone) |
| Total number of polymer chains | 4 |
| Total formula weight | 711068.85 |
| Authors | Jiang, Y.,Zhang, Z.,Toth, B.,Szollosi, A.,Csanady, L. (deposition date: 2024-09-13, release date: 2024-11-06, Last modification date: 2024-12-18) |
| Primary citation | Toth, B.,Jiang, Y.,Szollosi, A.,Zhang, Z.,Csanady, L. A conserved mechanism couples cytosolic domain movements to pore gating in the TRPM2 channel. Proc.Natl.Acad.Sci.USA, 121:e2415548121-e2415548121, 2024 Cited by PubMed Abstract: Transient Receptor Potential Melastatin 2 (TRPM2) cation channels contribute to immunocyte activation, insulin secretion, and central thermoregulation. TRPM2 opens upon binding cytosolic Ca and ADP ribose (ADPR). We present here the 2.5 Å cryo-electronmicroscopy structure of TRPM2 from (nvTRPM2) in a lipid nanodisc, complexed with Ca and ADPR-2'-phosphate. Comparison with nvTRPM2 without nucleotide reveals that nucleotide binding-induced movements in the protein's three "core" layers deconvolve into a set of rigid-body rotations conserved from cnidarians to man. By covalently crosslinking engineered cysteine pairs we systematically trap the cytosolic layers in specific conformations and study effects on gate opening/closure. The data show that nucleotide binding in Layer 3 disrupts inhibitory intersubunit interactions, allowing rotation of Layer 2 which in turn expands the gate located in Layer 1. Channels trapped in that "activated" state are no longer nucleotide dependent, but are opened by binding of Ca alone. PubMed: 39514307DOI: 10.1073/pnas.2415548121 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.52 Å) |
Structure validation
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