4OYU

Crystal structure of the N-terminal domains of muskelin

Summary for 4OYU

• Entry DOI: 10.2210/pdb4oyu/pdb
• Descriptor: Muskelin, 1,2-ETHANEDIOL, GLYCEROL, ... (4 entities in total)
• Functional Keywords: discoidin domain, lish motif, dimer, protein binding
• Biological source: Rattus norvegicus (Rat)
• Cellular location: Cytoplasm : Q99PV3
• Total number of polymer chains: 2
• Total formula weight: 47872.83

Authors

Delto, C.,Kuper, J.,Schindelin, H. (deposition date: 2014-02-13, release date: 2015-02-11, Last modification date: 2023-12-27)

Primary citation

Delto, C.F.,Heisler, F.F.,Kuper, J.,Sander, B.,Kneussel, M.,Schindelin, H.
The LisH Motif of Muskelin Is Crucial for Oligomerization and Governs Intracellular Localization.
Structure, 23:364-373, 2015

PubMed Abstract: Neurons regulate the number of surface receptors by balancing the transport to and from the plasma membrane to adjust their signaling properties. The protein muskelin was recently identified as a key factor guiding the transport of α1 subunit-containing GABAA receptors. Here we present the crystal structure of muskelin, comprising its N-terminal discoidin domain and Lis1-homology (LisH) motif. The molecule crystallized as a dimer with the LisH motif exclusively mediating oligomerization. Our subsequent biochemical analyses confirmed that the LisH motif acts as a dimerization element in muskelin. Together with an intermolecular head-to-tail interaction, the LisH-dependent dimerization is required to assemble a muskelin tetramer. Intriguingly, our cellular studies revealed that the loss of this dimerization results in a complete redistribution of muskelin from the cytoplasm to the nucleus and impairs muskelin's function in GABAA receptor transport. These studies demonstrate that the LisH-dependent dimerization is a crucial factor for muskelin function.

PubMed: 25579817
DOI: 10.1016/j.str.2014.11.016

Experimental method

X-RAY DIFFRACTION (1.8 Å)