5y31

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Crystal structure of human LGI1-ADAM22 complex

Structural highlights

5y31 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 7.125Å
Ligands:CA, NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ADA22_HUMAN Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein. Involved in regulation of cell adhesion and spreading and in inhibition of cell proliferation. Neuronal receptor for LGI1.[1] [2] [3]

Publication Abstract from PubMed

Epilepsy is a common brain disorder throughout history. Epilepsy-related ligand-receptor complex, LGI1-ADAM22, regulates synaptic transmission and has emerged as a determinant of brain excitability, as their mutations and acquired LGI1 autoantibodies cause epileptic disorders in human. Here, we report the crystal structure of human LGI1-ADAM22 complex, revealing a 2:2 heterotetrameric assembly. The hydrophobic pocket of the C-terminal epitempin-repeat (EPTP) domain of LGI1 binds to the metalloprotease-like domain of ADAM22. The N-terminal leucine-rich repeat and EPTP domains of LGI1 mediate the intermolecular LGI1-LGI1 interaction. A pathogenic R474Q mutation of LGI1, which does not exceptionally affect either the secretion or the ADAM22 binding, is located in the LGI1-LGI1 interface and disrupts the higher-order assembly of the LGI1-ADAM22 complex in vitro and in a mouse model for familial epilepsy. These studies support the notion that the LGI1-ADAM22 complex functions as the trans-synaptic machinery for precise synaptic transmission.

Structural basis of epilepsy-related ligand-receptor complex LGI1-ADAM22.,Yamagata A, Miyazaki Y, Yokoi N, Shigematsu H, Sato Y, Goto-Ito S, Maeda A, Goto T, Sanbo M, Hirabayashi M, Shirouzu M, Fukata Y, Fukata M, Fukai S Nat Commun. 2018 Apr 18;9(1):1546. doi: 10.1038/s41467-018-03947-w. PMID:29670100[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
8 reviews cite this structure
Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous system.
Hsia et al. (2019)
7 more
21 other articles
No citations found

See Also

References

  1. ↑ Zhu P, Sun Y, Xu R, Sang Y, Zhao J, Liu G, Cai L, Li C, Zhao S. The interaction between ADAM 22 and 14-3-3zeta: regulation of cell adhesion and spreading. Biochem Biophys Res Commun. 2003 Feb 21;301(4):991-9. PMID:12589811
  2. ↑ Zhu P, Sang Y, Xu H, Zhao J, Xu R, Sun Y, Xu T, Wang X, Chen L, Feng H, Li C, Zhao S. ADAM22 plays an important role in cell adhesion and spreading with the assistance of 14-3-3. Biochem Biophys Res Commun. 2005 Jun 17;331(4):938-46. PMID:15882968 doi:http://dx.doi.org/10.1016/j.bbrc.2005.03.229
  3. ↑ D'Abaco GM, Ng K, Paradiso L, Godde NJ, Kaye A, Novak U. ADAM22, expressed in normal brain but not in high-grade gliomas, inhibits cellular proliferation via the disintegrin domain. Neurosurgery. 2006 Jan;58(1):179-86; discussion 179-86. PMID:16385342
  4. ↑ Yamagata A, Miyazaki Y, Yokoi N, Shigematsu H, Sato Y, Goto-Ito S, Maeda A, Goto T, Sanbo M, Hirabayashi M, Shirouzu M, Fukata Y, Fukata M, Fukai S. Structural basis of epilepsy-related ligand-receptor complex LGI1-ADAM22. Nat Commun. 2018 Apr 18;9(1):1546. doi: 10.1038/s41467-018-03947-w. PMID:29670100 doi:http://dx.doi.org/10.1038/s41467-018-03947-w

Contents


PDB ID 5y31

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OCA

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