Subtopic Deep Dive

V-ATPase Structure and Function
Research Guide

What is V-ATPase Structure and Function?

V-ATPase is a rotary proton pump consisting of V1 and V0 domains that acidifies organelles through ATP hydrolysis-driven proton translocation.

V-ATPase structure features a multi-subunit stator assembly stabilizing the central rotor during catalysis (Forgac, 2007). Research examines isoform diversity, lipid dependence, and V0-mediated proton transport. Over 1500 papers cite Forgac's 2007 review on its rotary mechanism.

Curated Papers

Key Challenges

Why It Matters

V-ATPases maintain lysosomal pH homeostasis critical for degradation and bone resorption by osteoclasts (Forgac, 2007). Bafilomycin A1 inhibition blocks autophagosome-lysosome fusion, revealing roles in autophagy (Yamamoto et al., 1998). Acidic microenvironments from V-ATPase activity promote tumor invasion (Kato et al., 2013). Dysregulation links to cancer progression via extracellular acidification.

Key Research Challenges

High-resolution V0 structure

Cryo-EM reveals partial V0 proton pathways but full rotary mechanism remains unresolved due to membrane complexity (Forgac, 2007). Lipid interactions challenge crystallization. Over 1580 citations highlight gaps in native assembly.

Isoform-specific functions

Tissue-specific isoforms vary in regulation but functional distinctions lack structural correlation (Forgac, 2007). Assembly and trafficking differences complicate targeting. Yamamoto et al. (1998) show isoform sensitivity to inhibitors.

Pathophysiological targeting

Inhibitors like bafilomycin disrupt acidification but lack selectivity for disease states (Yamamoto et al., 1998). Cancer relies on V-ATPase for survival in acidic environments (Kato et al., 2013). Forgac (2007) notes therapeutic potential unmet by specificity issues.

Essential Papers

Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.

John E. Walker, M Saraste, M J Runswick et al. · 1982 · The EMBO Journal · 5.3K citations

Assessing mitochondrial dysfunction in cells

Martin D. Brand, David G. Nicholls · 2011 · Biochemical Journal · 2.3K citations

Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands...

Extracellular ATP: effects, sources and fate

John L. Gordon · 1986 · Biochemical Journal · 1.7K citations

Research Article| January 15 1986 Extracellular ATP: effects, sources and fate J L Gordon J L Gordon Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1986) 233 (...

Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology

Michael Forgac · 2007 · Nature Reviews Molecular Cell Biology · 1.6K citations

A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth

Sébastien Bonnet, Stephen L. Archer, Joan Allalunis‐Turner et al. · 2007 · Cancer Cell · 1.5K citations

Targeting the dynamic HSP90 complex in cancer

Jane B. Trepel, Mehdi Mollapour, Giuseppe Giaccone et al. · 2010 · Nature reviews. Cancer · 1.5K citations

Disruption of Fusion Results in Mitochondrial Heterogeneity and Dysfunction

Hsiuchen Chen, Anne Chomyn, David C. Chan · 2005 · Journal of Biological Chemistry · 1.3K citations

Mitochondria undergo continual cycles of fusion and fission, and the balance of these opposing processes regulates mitochondrial morphology. Paradoxically, cells invest many resources to maintain t...

Reading Guide

Foundational Papers

Start with Forgac (2007) for rotary pump overview and physiology; Walker et al. (1982) for nucleotide binding fold evolution; Yamamoto et al. (1998) for functional inhibition assays.

Recent Advances

Kato et al. (2013) on cancer acidification; Jo et al. (2007) for membrane simulation tools applicable to V0.

Core Methods

Cryo-EM for structures (Forgac, 2007); bafilomycin inhibition (Yamamoto et al., 1998); MD simulations (Jo et al., 2007).

How PapersFlow Helps You Research V-ATPase Structure and Function

Discover & Search

Research Agent uses searchPapers and citationGraph on Forgac (2007) to map 1580+ citing works on V-ATPase rotary mechanisms, then exaSearch for cryo-EM structures and findSimilarPapers for lipid dependence studies.

Analyze & Verify

Analysis Agent applies readPaperContent to Yamamoto et al. (1998) for bafilomycin effects, verifyResponse with CoVe for inhibitor specificity claims, and runPythonAnalysis to quantify pH data from Kato et al. (2013) with statistical verification via GRADE scoring.

Synthesize & Write

Synthesis Agent detects gaps in isoform regulation from Forgac (2007) citations, flags contradictions in proton translocation models, while Writing Agent uses latexEditText, latexSyncCitations for Forgac (2007), and latexCompile to generate V-ATPase rotor diagrams via exportMermaid.

Use Cases

"Extract pH change data from V-ATPase inhibition papers and plot dose-response curves."

Research Agent → searchPapers('bafilomycin V-ATPase') → Analysis Agent → readPaperContent(Yamamoto 1998) → runPythonAnalysis(pandas/matplotlib dose-response plot) → researcher gets quantified inhibition curves with stats.

"Write a review section on V-ATPase structure with citations and rotary mechanism figure."

Research Agent → citationGraph(Forgac 2007) → Synthesis Agent → gap detection → Writing Agent → latexEditText(structure text) → latexSyncCitations → latexCompile → researcher gets compiled LaTeX PDF with Mermaid rotor diagram.

"Find GitHub repos with V-ATPase simulation code from structural biology papers."

Research Agent → searchPapers('V-ATPase cryo-EM simulation') → Code Discovery → paperExtractUrls → paperFindGithubRepo → githubRepoInspect → researcher gets verified MD simulation scripts linked to Jo et al. (2007) membrane tools.

Automated Workflows

Deep Research workflow scans 50+ V-ATPase papers via searchPapers, structures Forgac (2007) citations into taxonomy, and generates reports on stator assembly. DeepScan applies 7-step CoVe to verify proton translocation claims from Yamamoto et al. (1998). Theorizer builds hypotheses on isoform-lipid interactions from citationGraph.

Try Doxa for V-ATPase Structure and Function Research

Frequently Asked Questions

What defines V-ATPase structure?

V-ATPase comprises soluble V1 (ATP hydrolysis) and membrane V0 (proton translocation) domains connected by rotary stalks (Forgac, 2007).

What methods study V-ATPase function?

Cryo-EM resolves rotary states; bafilomycin A1 inhibits to probe acidification (Yamamoto et al., 1998); molecular dynamics simulates V0 with tools from Jo et al. (2007).

What are key papers on V-ATPase?

Forgac (2007, 1580 citations) reviews rotary physiology; Yamamoto et al. (1998, 1284 citations) details bafilomycin autophagy block; Walker et al. (1982, 5290 citations) identifies nucleotide folds.