Binding of Substrates to the Central Pore of the Vps4 ATPase Is Autoinhibited by the Microtubule Interacting and Trafficking (MIT) Domain and Activated by MIT Interacting Motifs (MIMs)

Han, Han; Monroe, Nicole; Votteler, Jörg; Shakya, Binita; Sundquist, Wesley I.; Hill, Christopher P.

doi:10.1074/jbc.m115.642355

Cited by 35 publications

(57 citation statements)

References 71 publications

(83 reference statements)

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“…CHMP3 has no Vps4-interacting MIM; however, CHMP3 and most other ESCRT-III subunits have sequences that bind to a range of other MIT domains from the Vps4 cofactor LIP5 (also known as Vta1 in yeast) 80, 81 , the deubiquitylating enzymes UBPY (also known as USP8), AMSH (also known as STAMBP) and Doa4 82 , and other proteins that are beyond the scope of this Review. Engagement of the MIT domain of VPS4 by MIM motifs potently activates ATP hydrolysis by the catalytic domain of VPS4 83–86 .…”

Section: Vps4: the Recycling Machinementioning

confidence: 99%

Reverse-topology membrane scission by the ESCRT proteins

Schöneberg

Lee

Iwasa

et al. 2016

Nat Rev Mol Cell Biol

370

419

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Preface The narrow membrane necks formed during viral, exosomal, and intra-endosomal budding from membranes, cytokinesis, and related processes have interiors that are contiguous with the cytosol. The severing of these necks involves action from the opposite face of the membrane as compared to the well-characterized coated vesicle pathways, and is referred to as “reverse” or “inverse” topology membrane scission. This process is carried out by the endosomal sorting complexes required for transport (ESCRT) proteins. In particular, the ESCRT-III proteins can form filaments, flat spirals, tubes and conical funnels, which are thought to somehow direct membrane remodeling and scission. Their assembly, and their disassembly by the ATPase VPS4, has been intensively studied, but the mechanism of scission has been elusive. New insights from cryo-electron microscopy and various types of spectroscopy may finally be close to rectifying this situation.

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Section: Vps4: the Recycling Machinementioning

confidence: 99%

Reverse-topology membrane scission by the ESCRT proteins

Schöneberg

Lee

Iwasa

et al. 2016

Nat Rev Mol Cell Biol

370

419

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“…MIT domains are three-helix bundles that bind different ESCRT-III tails in a remarkable variety of ways (Figure 2 c ). ESCRT-III substrate engagement activates the enzyme by relieving autoinhibitory MIT domain interactions (Babst et al 2011, Han et al 2015, Merrill & Hanson 2010). The Vps4 hexamer can then assemble about ESCRT-III elements located upstream of the terminal MIT binding site (Han et al 2015, 2017; Monroe et al 2017; Shim et al 2008), yielding an active holoenzyme.…”

Section: Vps4 and Related Aaa Atpasesmentioning

confidence: 99%

Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

McCullough

Frost

Sundquist

2018

Annu. Rev. Cell Dev. Biol.

Self Cite

222

272

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The endosomal sorting complexes required for transport (ESCRT) pathway mediates cellular membrane remodeling and fission reactions. The pathway comprises five core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble complexes are typically recruited to target membranes by site-specific adaptors that bind one or both of the early-acting ESCRT factors: ALIX and ESCRT-I/ESCRT-II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane-bound filaments that recruit the AAA ATPase Vps4. Together, ESCRT-III filaments and Vps4 remodel and sever membranes. Here, we review recent advances in our understanding of the structures, activities, and mechanisms of the ESCRT-III and Vps4 machinery, including the first high-resolution structures of ESCRT-III filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside-in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated membrane fission.

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“…To investigate the role that nucleotide state plays in directing this subdomain positioning, we structurally characterized hex YME1 WT in the absence of nucleotide, as well as in the presence of ADPAlF X , an ATP analog known to induce ATP-hydrolysis-intermediate states in other AAA+ ATPases (45, 46). Notably, in both the absence of ATP and presence of ADPAlF X , the conformational heterogeneity of the hexamer rose to a level that impeded 3D reconstructions.…”

Section: Nucleotide State Coordinates Major Structural Rearrangementsmentioning

confidence: 99%

Structure of the mitochondrial inner membrane AAA+ protease YME1 gives insight into substrate processing

Puchades

Rampello

Shin

et al. 2017

Science

201

264

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We present the first atomic model of a substrate-bound inner mitochondrial membrane AAA+ quality control protease, YME1. Our ~3.4 Å cryo-EM structure reveals how the ATPases form a closed spiral staircase encircling an unfolded substrate, directing it toward the flat, symmetric protease ring. Importantly, the structure reveals how three coexisting nucleotide states allosterically induce distinct positioning of tyrosines in the central channel, resulting in substrate engagement and translocation to the negatively charged proteolytic chamber. This tight coordination by a network of conserved residues defines a sequential, around-the-ring ATP hydrolysis cycle that results in step-wise substrate translocation. Furthermore, we identify a hinge-like linker that accommodates the large-scale nucleotide-driven motions of the ATPase spiral independently of the contiguous planar proteolytic base. These results define the first molecular mechanism for a mitochondrial inner membrane AAA+ protease and reveal a translocation mechanism likely conserved for other AAA+ ATPases.

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Binding of Substrates to the Central Pore of the Vps4 ATPase Is Autoinhibited by the Microtubule Interacting and Trafficking (MIT) Domain and Activated by MIT Interacting Motifs (MIMs)

Cited by 35 publications

References 71 publications

Reverse-topology membrane scission by the ESCRT proteins

Reverse-topology membrane scission by the ESCRT proteins

Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

Structure of the mitochondrial inner membrane AAA+ protease YME1 gives insight into substrate processing

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