Structural Insights into the Unusually Strong ATPase Activity of the AAA Domain of the Caenorhabditis elegans Fidgetin-like 1 (FIGL-1) Protein

Peng, Wentao; Lin, Zhijie; Lü, Jing; Shen, Yuequan; Wang, Chunguang

doi:10.1074/jbc.m113.502559

Cited by 19 publications

(28 citation statements)

References 37 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The small subdomain comprises a four-helix bundle; in some meiotic clade AAA ATPases functionally important insertions are found between the third and fourth helices of the small subdomain (Peng et al, 2013; Scott et al, 2005). In Msp1, the third helix protrudes from the bundle by virtue of a ~2 turn extension relative to the corresponding helix in closely related homologs (Figure S2); however, the functional significance of this remains unclear, since there is little sequence conservation in this region among Msp1 homologs.…”

Section: Resultsmentioning

confidence: 99%

Msp1 Is a Membrane Protein Dislocase for Tail-Anchored Proteins

et al. 2017

View full text Add to dashboard Cite

Mislocalized tail-anchored (TA) proteins of the outer mitochondrial membrane are cleared by a newly identified quality control pathway involving the conserved eukaryotic protein Msp1 (ATAD1 in humans). Msp1 is a transmembrane AAA-ATPase but its role in TA protein clearance is not known. Here, using purified components reconstituted into proteoliposomes we show that Msp1 is both necessary and sufficient to drive the ATP-dependent extraction of TA proteins from the membrane. A crystal structure of the Msp1 cytosolic region modeled into a ring hexamer suggests that active Msp1 contains a conserved membrane-facing surface adjacent to a central pore. Structure-guided mutagenesis of the pore residues shows they are critical for TA protein extraction in vitro and for functional complementation of an Msp1 deletion in yeast. Together these data provide a molecular framework for Msp1-dependent extraction of mislocalized TA proteins from the outer mitochondrial membrane.

show abstract

Section: Resultsmentioning

confidence: 99%

Msp1 Is a Membrane Protein Dislocase for Tail-Anchored Proteins

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Crystal structures of human, yeast and archaeal Vps4 24; 104; 105; 106; 107 , human and D. melanogaster Spastin 108; 109 , and C. elegans Fidgetin-like protein 1 (FIGL-1) 110 , have revealed details of the domain structure (Figure 4). The large AAA ATPase domain contains 5 α-helices that are arranged on either side of a central 5-stranded parallel β-sheet.…”

Section: Aaa Atpase Cassettementioning

confidence: 99%

“…Crystal structures of (a) human VPS4B (PDB ID: 1XWI) 24 , (b) human spastin (PDB ID: 3VFD) 109 and (c) human fidgetin-like 1 (FIGL-1, PDB ID: 3D8B) 110 . Coloring is as in Figure 1.…”

Section: Figurementioning

confidence: 99%

Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines

Monroe

Hill

2016

Journal of Molecular Biology

View full text Add to dashboard Cite

Meiotic clade AAA ATPases, which were initially grouped on the basis of phylogenetic classification of their AAA ATPase cassette, include four relatively well characterized family members, Vps4, spastin, katanin, and fidgetin. These enzymes all function to disassemble specific polymeric protein structures, with Vps4 disassembling the ESCRT-III polymers that are central to the many membrane-remodeling activities of the ESCRT pathway, and spastin, katanin p60 and fidgetin affecting multiple aspects of cellular dynamics by severing microtubules. They share a common domain architecture that features an N-terminal MIT domain followed by a single AAA ATPase cassette. Meiotic clade AAA ATPases function as hexamers that can cycle between the active assembly and inactive monomers/dimers in a regulated process, and appear to disassemble their polymeric substrates by translocating subunits through the central pore of their hexameric ring. Recent studies with Vps4 have shown that nucleotide-induced asymmetry is a requirement for substrate binding to the pore loops, and that recruitment to the protein lattice via MIT domains also relieves auto-inhibition and primes the AAA ATPase cassettes for substrate binding. The most striking, unifying feature of meiotic clade AAA ATPases may be their MIT domain, which is a module that is found in a wide variety of proteins that localize to ESCRT-III polymers. Spastin also displays an adjacent microtubule-binding sequence, and the presence of both ESCRT-III and microtubule binding elements may underlie the recent findings that the ESCRT-III disassembly function of Vps4 and the microtubule-severing function of spastin, and potentially katanin and fidgetin, are highly coordinated.

show abstract

“…B). The short helix α9a was initially observed in the structure of the AAA domain of C. elegans fidgetin‐like 1 protein, and mutations in this helix affected notably the protein hexamerization and ATPase activity . In spastin, helix α9a also participates in the intersubunit interaction (Fig.…”

Section: Resultsmentioning

confidence: 98%

The AAA protein spastin possesses two levels of basal ATPase activity

et al. 2018

Self Cite

View full text Add to dashboard Cite

The AAA ATPase spastin is a microtubule-severing enzyme that plays important roles in various cellular events including axon regeneration. Herein, we found that the basal ATPase activity of spastin is negatively regulated by spastin concentration. By determining a spastin crystal structure, we demonstrate the necessity of intersubunit interactions between spastin AAA domains. Neutralization of the positive charges in the microtubule-binding domain (MTBD) of spastin dramatically decreases the ATPase activity at low concentration, although the ATP-hydrolyzing potential is not affected. These results demonstrate that, in addition to the AAA domain, the MTBD region of spastin is also involved in regulating ATPase activity, making interactions between spastin protomers more complicated than expected.

show abstract

Structural Insights into the Unusually Strong ATPase Activity of the AAA Domain of the Caenorhabditis elegans Fidgetin-like 1 (FIGL-1) Protein

Cited by 19 publications

References 37 publications

Msp1 Is a Membrane Protein Dislocase for Tail-Anchored Proteins

Msp1 Is a Membrane Protein Dislocase for Tail-Anchored Proteins

Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines

The AAA protein spastin possesses two levels of basal ATPase activity

Contact Info

Product

Resources

About