4TVS

LAP1(aa356-583), H.sapiens, bound to VHH-BS1

Summary for 4TVS

• Entry DOI: 10.2210/pdb4tvs/pdb
• Descriptor: Torsin-1A-interacting protein 1, VHH Domain BS-1, SULFATE ION, ... (5 entities in total)
• Functional Keywords: nuclear envelope protein, aaa+-associated, activator, membrane protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus inner membrane ; Single-pass membrane protein : Q5JTV8
• Total number of polymer chains: 4
• Total formula weight: 81846.99

Authors

Sosa, B.A.,Schwartz, T.U. (deposition date: 2014-06-27, release date: 2014-09-03, Last modification date: 2024-10-16)

Primary citation

Sosa, B.A.,Demircioglu, F.E.,Chen, J.Z.,Ingram, J.,Ploegh, H.L.,Schwartz, T.U.
How lamina-associated polypeptide 1 (LAP1) activates Torsin.
Elife, 3:e03239-e03239, 2014

PubMed Abstract: Lamina-associated polypeptide 1 (LAP1) resides at the nuclear envelope and interacts with Torsins, poorly understood endoplasmic reticulum (ER)-localized AAA+ ATPases, through a conserved, perinuclear domain. We determined the crystal structure of the perinuclear domain of human LAP1. LAP1 possesses an atypical AAA+ fold. While LAP1 lacks canonical nucleotide binding motifs, its strictly conserved arginine 563 is positioned exactly where the arginine finger of canonical AAA+ ATPases is found. Based on modeling and electron microscopic analysis, we propose that LAP1 targets Torsin to the nuclear envelope by forming an alternating, heterohexameric (LAP1-Torsin)3 ring, in which LAP1 acts as the Torsin activator. The experimental data show that mutation of arginine 563 in LAP1 reduces its ability to stimulate TorsinA ATPase hydrolysis. This knowledge may help scientists understand the etiology of DYT1 primary dystonia, a movement disorder caused by a single glutamate deletion in TorsinA.

PubMed: 25149450
DOI: 10.7554/eLife.03239

Experimental method

X-RAY DIFFRACTION (1.6 Å)