scholarly journals Structural Basis of Molecular Recognition between ESCRT-III-like Protein Vps60 and AAA-ATPase Regulator Vta1 in the Multivesicular Body Pathway

2012 ◽  
Vol 287 (52) ◽  
pp. 43899-43908 ◽  
Author(s):  
Zhongzheng Yang ◽  
Cody Vild ◽  
Jiaying Ju ◽  
Xu Zhang ◽  
Jianping Liu ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Multivesicular Body ◽  
Structural Basis ◽  
Aaa Atpase

scholarly journals Structural Basis of Ist1 Function and Ist1–Did2 Interaction in the Multivesicular Body Pathway and Cytokinesis

2009 ◽  
Vol 20 (15) ◽  
pp. 3514-3524 ◽  
Author(s):  
Junyu Xiao ◽  
Xiao-Wei Chen ◽  
Brian A. Davies ◽  
Alan R. Saltiel ◽  
David J. Katzmann ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Mechanism Of Action ◽  
Intramolecular Interaction ◽  
Multivesicular Body ◽  
Structural Motif ◽  
Structural Basis ◽  
Membrane Deformation ◽  
Aaa Atpase ◽  
Cellular Processes ◽  
Escrt Machinery

The ESCRT machinery functions in several important eukaryotic cellular processes. The AAA-ATPase Vps4 catalyzes disassembly of the ESCRT-III complex and may regulate membrane deformation and vesicle scission as well. Ist1 was proposed to be a regulator of Vps4, but its mechanism of action was unclear. The crystal structure of the N-terminal domain of Ist1 (Ist1NTD) reveals an ESCRT-III subunit-like fold, implicating Ist1 as a divergent ESCRT-III family member. Ist1NTD specifically binds to the ESCRT-III subunit Did2, and cocrystallization of Ist1NTD with a Did2 fragment shows that Ist1 interacts with the Did2 C-terminal MIM1 (MIT-interacting motif 1) via a novel MIM-binding structural motif. This arrangement indicates a mechanism for intermolecular ESCRT-III subunit association and may also suggest one form of ESCRT-III subunit autoinhibition via intramolecular interaction.

scholarly journals Structural basis for molecular recognition of folic acid by folate receptors

Nature ◽  
2013 ◽  
Vol 500 (7463) ◽  
pp. 486-489 ◽  
Author(s):  
Chen Chen ◽  
Jiyuan Ke ◽  
X. Edward Zhou ◽  
Wei Yi ◽  
Joseph S. Brunzelle ◽  
...  
Keyword(s):  
Folic Acid ◽  
Molecular Recognition ◽  
Structural Basis ◽  
Folate Receptors

scholarly journals Novel Interactions of ESCRT-III with LIP5 and VPS4 and their Implications for ESCRT-III Disassembly

2008 ◽  
Vol 19 (6) ◽  
pp. 2661-2672 ◽  
Author(s):  
Soomin Shim ◽  
Samuel A. Merrill ◽  
Phyllis I. Hanson
Keyword(s):  
Atpase Activity ◽  
Binding Site ◽  
Binding Sites ◽  
Essential Role ◽  
Multivesicular Body ◽  
The Other ◽  
Aaa Atpase ◽  
Direct Binding ◽  
Novel Interactions

The AAA+ ATPase VPS4 plays an essential role in multivesicular body biogenesis and is thought to act by disassembling ESCRT-III complexes. VPS4 oligomerization and ATPase activity are promoted by binding to LIP5. LIP5 also binds to the ESCRT-III like protein CHMP5/hVps60, but how this affects its function remains unclear. Here we confirm that LIP5 binds tightly to CHMP5, but also find that it binds well to additional ESCRT-III proteins including CHMP1B, CHMP2A/hVps2–1, and CHMP3/hVps24 but not CHMP4A/hSnf7–1 or CHMP6/hVps20. LIP5 binds to a different region within CHMP5 than within the other ESCRT-III proteins. In CHMP1B and CHMP2A, its binding site encompasses sequences at the proteins' extreme C-termini that overlap with “MIT interacting motifs” (MIMs) known to bind to VPS4. We find unexpected evidence of a second conserved binding site for VPS4 in CHMP2A and CHMP1B, suggesting that LIP5 and VPS4 may bind simultaneously to these proteins despite the overlap in their primary binding sites. Finally, LIP5 binds preferentially to soluble CHMP5 but instead to polymerized CHMP2A, suggesting that the newly defined interactions between LIP5 and ESCRT-III proteins may be regulated by ESCRT-III conformation. These studies point to a role for direct binding between LIP5 and ESCRT-III proteins that is likely to complement LIP5's previously described ability to regulate VPS4 activity.

scholarly journals VPS37A directs ESCRT recruitment for phagophore closure

2019 ◽  
Vol 218 (10) ◽  
pp. 3336-3354 ◽  
Author(s):  
Yoshinori Takahashi ◽  
Xinwen Liang ◽  
Tatsuya Hattori ◽  
Zhenyuan Tang ◽  
Haiyan He ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Growth Factor Receptor ◽  
Multivesicular Body ◽  
Regulatory Mechanisms ◽  
Endosomal Sorting ◽  
Aaa Atpase ◽  
Escrt Machinery ◽  
Genome Wide ◽  
A Genome ◽  
Epidermal Growth

The process of phagophore closure requires the endosomal sorting complex required for transport III (ESCRT-III) subunit CHMP2A and the AAA ATPase VPS4, but their regulatory mechanisms remain unknown. Here, we establish a FACS-based HaloTag-LC3 autophagosome completion assay to screen a genome-wide CRISPR library and identify the ESCRT-I subunit VPS37A as a critical component for phagophore closure. VPS37A localizes on the phagophore through the N-terminal putative ubiquitin E2 variant domain, which is found to be required for autophagosome completion but dispensable for ESCRT-I complex formation and the degradation of epidermal growth factor receptor in the multivesicular body pathway. Notably, loss of VPS37A abrogates the phagophore recruitment of the ESCRT-I subunit VPS28 and CHMP2A, whereas inhibition of membrane closure by CHMP2A depletion or VPS4 inhibition accumulates VPS37A on the phagophore. These observations suggest that VPS37A coordinates the recruitment of a unique set of ESCRT machinery components for phagophore closure in mammalian cells.

Structural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4

Nature ◽  
2007 ◽  
Vol 449 (7163) ◽  
pp. 735-739 ◽  
Author(s):  
Takayuki Obita ◽  
Suraj Saksena ◽  
Sara Ghazi-Tabatabai ◽  
David J. Gill ◽  
Olga Perisic ◽  
...  
Keyword(s):  
Selective Recognition ◽  
Structural Basis ◽  
Aaa Atpase

scholarly journals Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael Prattes ◽  
Irina Grishkovskaya ◽  
Victor-Valentin Hodirnau ◽  
Ingrid Rössler ◽  
Isabella Klein ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Atp Hydrolysis ◽  
Ribosomal Subunit ◽  
Covalent Bond ◽  
Resistance Mechanisms ◽  
Drug Binding ◽  
Structural Basis ◽  
Aaa Atpase ◽  
Maturation Factor ◽  
Key Factor

AbstractThe hexameric AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis and initiates cytoplasmic maturation of the large ribosomal subunit by releasing the shuttling maturation factor Rlp24. Drg1 monomers contain two AAA-domains (D1 and D2) that act in a concerted manner. Rlp24 release is inhibited by the drug diazaborine which blocks ATP hydrolysis in D2. The mode of inhibition was unknown. Here we show the first cryo-EM structure of Drg1 revealing the inhibitory mechanism. Diazaborine forms a covalent bond to the 2′-OH of the nucleotide in D2, explaining its specificity for this site. As a consequence, the D2 domain is locked in a rigid, inactive state, stalling the whole Drg1 hexamer. Resistance mechanisms identified include abolished drug binding and altered positioning of the nucleotide. Our results suggest nucleotide-modifying compounds as potential novel inhibitors for AAA-ATPases.

scholarly journals Structural basis for the molecular recognition of polyadenosine RNA by Nab2 Zn fingers

2013 ◽  
Vol 42 (1) ◽  
pp. 672-680 ◽  
Author(s):  
Sonja I. Kuhlmann ◽  
Eugene Valkov ◽  
Murray Stewart
Keyword(s):  
Molecular Recognition ◽  
Structural Basis

scholarly journals Structural Basis of ATP Hydrolysis and Intersubunit Signaling in the AAA+ ATPase p97

Structure ◽  
2016 ◽  
Vol 24 (1) ◽  
pp. 127-139 ◽  
Author(s):  
Petra Hänzelmann ◽  
Hermann Schindelin
Keyword(s):  
Atp Hydrolysis ◽  
Structural Basis ◽  
Aaa Atpase

scholarly journals Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1

2006 ◽  
Vol 172 (5) ◽  
pp. 705-717 ◽  
Author(s):  
Ishara Azmi ◽  
Brian Davies ◽  
Christian Dimaano ◽  
Johanna Payne ◽  
Debra Eckert ◽  
...  
Keyword(s):  
Protein Composition ◽  
Surface Protein ◽  
Multivesicular Body ◽  
Proper Function ◽  
Cellular Functions ◽  
Endosomal Sorting ◽  
Aaa Atpase ◽  
Evolutionarily Conserved

In eukaryotes, the multivesicular body (MVB) sorting pathway plays an essential role in regulating cell surface protein composition, thereby impacting numerous cellular functions. Vps4, an ATPase associated with a variety of cellular activities, is required late in the MVB sorting reaction to dissociate the endosomal sorting complex required for transport (ESCRT), a requisite for proper function of this pathway. However, regulation of Vps4 function is not understood. We characterize Vta1 as a positive regulator of Vps4 both in vivo and in vitro. Vta1 promotes proper assembly of Vps4 and stimulates its ATPase activity through the conserved Vta1/SBP1/LIP5 region present in Vta1 homologues across evolution, including human SBP1 and Arabidopsis thaliana LIP5. These results suggest an evolutionarily conserved mechanism through which the disassembly of the ESCRT proteins, and thereby MVB sorting, is regulated by the Vta1/SBP1/LIP5 proteins.

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