GO:0051117 ATPase binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0051117 ATPase binding is a molecular function defined as binding to an ATPase, any enzyme that catalyzes ATP hydrolysis.
• ATPase binding underlies diverse processes including metal transport, proteasomal degradation, and bacterial defence [2,5,7].
• Key ATPase families include P-type ATPases (e.g., ATP7B, CopA), V-ATPases, and AAA+ ATPases [1,2,8].
• Dysregulation of ATPase binding is linked to Wilson disease, cancer, and neurodegeneration [2,8].
• CRISPR knockout, point mutation, knock-in, and overexpression models enable functional dissection of ATPase binding [5,7].
• EDITGENE provides end-to-end CRISPR services to study ATPase binding in any cell type.
Description
ATPase binding (GO:0051117) is a molecular function describing the selective interaction of a protein or molecule with an ATPase, an enzyme that hydrolyzes ATP. This binding event is fundamental to numerous cellular processes, from ion transport to protein degradation [2,5]. Understanding ATPase binding is critical because it regulates the activity, localization, and substrate specificity of ATPases, which are implicated in a wide range of diseases [2,8]. Researchers study ATPase binding to uncover mechanisms of energy transduction, metal homeostasis, and drug resistance [1,3,8]. The term encompasses binding to various ATPase classes, including P-type, V-type, and AAA+ ATPases, each with distinct structural and functional features [1,2,5].
ATPase binding At A Glance
| GO ID | GO:0051117 |
|---|---|
| GO term | ATPase binding |
| Ontology | molecular_function |
| Synonym | None |
| Major function | Binding to ATPases, modulating their activity or assembly |
| Examples of ATPases | P-type ATPases (ATP7B, CopA), V-ATPase, proteasomal ATPases |
| Related diseases | Wilson disease, cancer, bacterial infections |
| Research methods | CRISPR screens, co-immunoprecipitation, ATPase activity assays |
What Is GO:0051117?
GO:0051117 ATPase binding is defined as the binding to an ATPase, any enzyme that catalyzes the hydrolysis of ATP. This molecular function does not include the catalytic activity itself but rather the physical interaction with an ATPase enzyme, which may modulate its activity, stability, or localization.
Why Is ATPase binding Important in Cell Biology?
ATPase binding is essential for regulating ATPase function in health and disease. Many ATPases are drug targets, and their binding partners influence drug efficacy and resistance [1,3]. For example, the V-ATPase E subunit mediates Cry2Ab toxin binding in insects, impacting pest control. In humans, mutations in the copper-transporting ATPase ATP7B cause Wilson disease, and its binding interactions are critical for copper homeostasis [2,8]. Thus, understanding ATPase binding provides insights into basic biology and therapeutic development.
• Regulates ATPase activity in ion transport and pH homeostasis [1,4].
• Mediates metal resistance and homeostasis via P-type ATPases [2,8].
• Controls proteasomal degradation through AAA+ ATPase interactions.
• Involved in bacterial defence systems such as PARIS.
• Implicated in Wilson disease via ATP7B binding defects.
• Potential target for insecticides like Cry2Ab.
• Affects cancer cell survival through V-ATPase interactions.
• Enables allosteric regulation of ATPases.
• Provides a basis for designing ATPase inhibitors.
• Facilitates structural studies of ATPase complexes.
Molecular Mechanism of ATPase binding
Binding to P-type ATPases
In simple terms: P-type ATPases are pumps that move ions across membranes, and other proteins can bind to them to control their activity.
P-type ATPases, such as ATP7B and CopA, undergo conformational changes during their catalytic cycle, and binding partners can stabilize specific states [2,8]. The copper-binding domains of ATP7B interact with copper, influencing its transport function. In Archaeoglobus fulgidus, the Cu+-ATPase CopA has metal-binding domains that are essential for function, and their interactions with the ATPase core regulate copper efflux.
Binding to V-ATPases
In simple terms: V-ATPases are rotary motors that pump protons, and binding to their subunits can affect their assembly or activity.
The V-ATPase E subunit binds to Cry2Ab toxin in Helicoverpa armigera, mediating toxicity. This interaction is specific and required for the insecticidal activity of Cry2Ab, highlighting the role of ATPase binding in host-pathogen interactions.
Binding to proteasomal ATPases
In simple terms: Proteasomal ATPases use ATP to unfold and translocate proteins into the proteasome for degradation, and binding between subunits coordinates this process.
ATP binding to neighbouring subunits of the proteasomal ATPase induces intersubunit allosteric coupling, essential for substrate processing. This cooperative binding ensures efficient protein degradation.
Binding to bacterial defence ATPases
In simple terms: Bacteria have defence systems that use ATPases to fight off viruses, and binding to these ATPases activates the defence.
The PARIS defence system relies on ATPase binding to activate its antiviral response. The architecture and activation mechanism involve ATPase interactions that trigger a cascade of events.
Structural basis of ATPase binding
In simple terms: The 3D structure of ATPases reveals how other molecules can bind to them.
The structure of Mg-ATPase nucleotide-binding domain at 1.6 Å resolution revealed a unique ATP-binding motif, providing insights into how binding partners might interact. Such structural data are crucial for understanding ATPase binding specificity.
Key Genes Involved in GO:0051117 ATPase binding
The following genes encode ATPases or proteins that bind to ATPases, as supported by the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ATP7B | Copper-transporting P-type ATPase | Wilson disease; metal binding studies |
| CopA | Copper-transporting ATPase | Bacterial copper resistance |
| ArsA | Arsenite-transporting ATPase | Mechanism of arsenite resistance |
| V-ATPase E | V-ATPase subunit | Cry2Ab toxicity in insects |
| Proteasomal ATPase | AAA+ ATPase in 19S proteasome | Protein degradation; allosteric regulation |
| Mg-ATPase | Magnesium-dependent ATPase | Structural studies of ATP binding |
| PARIS ATPase | Bacterial defence ATPase | Antiviral defence mechanisms |
| Mitochondrial ATPase | ATP synthase | Energy metabolism |
| ATP7A | Copper-transporting ATPase | Menkes disease (implied by analogy to ATP7B) |
| ATP2A1 | SERCA calcium ATPase | Muscle contraction (implied by general ATPase function) |
| ATP1A1 | Na+/K+ ATPase | Ion homeostasis (implied by general ATPase function) |
| ATP6V1A | V-ATPase catalytic subunit | Proton transport (implied by V-ATPase function) |
| ATP13A2 | P-type ATPase | Neurodegeneration (implied by P-type ATPase role) |
| ATP8B1 | P-type ATPase | Cholestasis (implied by P-type ATPase role) |
| ATP2B1 | Plasma membrane calcium ATPase | Calcium signaling (implied by general ATPase function) |
| ATP5F1A | Mitochondrial ATP synthase subunit | Energy metabolism |
| ATP6AP1 | V-ATPase accessory protein | V-ATPase assembly (implied by V-ATPase function) |
How Is ATPase binding Regulated?
ATPase binding is regulated by factors such as ATP concentration, post-translational modifications, and allosteric interactions. For example, ATP binding to proteasomal ATPase subunits induces conformational changes that promote intersubunit coupling. In P-type ATPases, metal binding to regulatory domains modulates ATPase activity [2,8]. The PARIS defence system is activated by ATPase binding upon phage infection. These regulatory mechanisms ensure precise control of ATPase function in response to cellular signals.
ATPase binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ATP7B | Wilson disease | Knockout hepatocyte cell line |
| CopA | Bacterial copper resistance | Bacterial knockout |
| V-ATPase E | Insecticidal toxicity | Insect cell overexpression |
| Proteasomal ATPase | Cancer (proteasome inhibition) | Knockout cancer cell line |
| PARIS ATPase | Bacterial defence | Bacterial knockout |
Wilson Disease and Copper Metabolism
Mutations in ATP7B, a copper-transporting P-type ATPase, cause Wilson disease, a disorder of copper overload. The metal-binding domains of ATP7B are critical for its function, and impaired binding leads to defective copper excretion. Studies of CopA, a bacterial homolog, provide insights into the mechanism of copper transport and resistance.
Cancer and V-ATPase
V-ATPases are involved in cancer progression by acidifying the tumor microenvironment. The V-ATPase E subunit mediates binding to Cry2Ab toxin in insects, but in humans, V-ATPase interactions are implicated in drug resistance. Targeting ATPase binding may offer therapeutic strategies.
Neurodegeneration and P-type ATPases
P-type ATPases such as ATP13A2 are linked to neurodegeneration. Although direct evidence from the cited papers is limited, the general role of ATPase binding in maintaining ion homeostasis suggests relevance [2,4].
From ATPase binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does ATP7B mutation affect copper transport? | Point mutation knock-in in HepG2 cells |
| What is the role of V-ATPase E in Cry2Ab toxicity? | Knockout in Helicoverpa armigera cells |
| How does ATP binding regulate proteasomal ATPase? | Point mutation in proteasomal ATPase subunits |
| Can CopA knockout increase copper sensitivity? | Knockout in Archaeoglobus fulgidus |
| What is the activation mechanism of PARIS? | Knock-in of tagged ATPase in bacteria |
| Does overexpression of ATP7B enhance copper efflux? | Overexpression in mammalian cells |
How to Study the ATPase binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Co-IP | Protein-protein interactions | Detect ATPase binding partners |
| ATPase activity assay | ATP hydrolysis rate | Measure modulation by binding |
| X-ray crystallography | 3D structure | Visualize binding interfaces |
| Cryo-EM | Macromolecular structure | Study large ATPase complexes |
| CRISPR knockout | Gene function | Identify genes affecting ATPase binding |
| Western blot | Protein expression | Validate knockout/overexpression |
| Immunofluorescence | Protein localization | Assess ATPase localization |
| Surface plasmon resonance | Binding affinity | Quantify ATPase-ligand interactions |
Co-immunoprecipitation and Pull-down
Co-immunoprecipitation (co-IP) and pull-down assays are used to detect physical interactions between ATPases and their binding partners. For example, the interaction between V-ATPase E and Cry2Ab was demonstrated using binding assays. These methods are essential for validating ATPase binding in vitro and in vivo.
ATPase Activity Assays
ATPase activity assays measure the rate of ATP hydrolysis, which can be modulated by binding partners. The mechanism of ArsA ATPase was elucidated using such assays. These assays help quantify the functional impact of binding events.
Structural Biology
X-ray crystallography and cryo-EM provide atomic-level insights into ATPase binding interfaces. The structure of Mg-ATPase nucleotide-binding domain revealed a unique ATP-binding motif. The architecture of the PARIS defence system was resolved by cryo-EM.
CRISPR Screening
Genome-wide CRISPR screens can identify genes that regulate ATPase binding. Although not directly cited, this approach is widely used to study ATPase-related pathways.
How CRISPR Can Be Used to Study GO:0051117 ATPase binding
Knockout
CRISPR knockout of ATPase genes or their binding partners can reveal loss-of-function phenotypes. For example, knocking out V-ATPase E in insect cells would test its role in Cry2Ab toxicity. Knockout of CopA in bacteria can assess copper resistance.
Point Mutation
Point mutations can dissect specific binding residues. Mutating the metal-binding domains of ATP7B can clarify their role in copper transport. Similarly, point mutations in proteasomal ATPase subunits can test allosteric coupling.
Knock-in
Knock-in of tagged ATPases allows visualization and purification of binding complexes. Tagging PARIS ATPase can help study its activation mechanism. Knock-in of fluorescent tags into ATP7B enables live-cell imaging.
Overexpression
Overexpression of ATPases or binding partners can enhance or disrupt interactions. Overexpressing ATP7B in cells can increase copper efflux. Overexpression of V-ATPase E may increase Cry2Ab binding.
How EDITGENE Supports ATPase binding Research
Researchers studying ATPase binding-related genes often need to determine whether a candidate gene is causally involved in a specific pathway or disease. EDITGENE provides comprehensive CRISPR services to generate precisely engineered cell models, enabling functional validation of ATPase binding mechanisms.
Contact EDITGENE today to design your custom CRISPR model for ATPase binding research.
Frequently Asked Questions About ATPase binding
What is ATPase binding?
ATPase binding (GO:0051117) is the molecular function of selectively interacting with an ATPase enzyme, which hydrolyzes ATP.
What genes are involved in ATPase binding?
Genes encoding ATPases such as ATP7B, CopA, and V-ATPase subunits, as well as their binding partners, are involved [1,2,8].
How is ATPase binding studied?
Common methods include co-immunoprecipitation, ATPase activity assays, and structural biology techniques like X-ray crystallography [1,3,6].
What diseases are associated with ATPase binding?
Wilson disease (ATP7B), cancer (V-ATPase), and bacterial infections (CopA) are linked to ATPase binding defects [1,2,8].
What is the role of ATPase binding in proteasome function?
ATP binding to proteasomal ATPase subunits induces allosteric coupling, essential for protein degradation.
Can CRISPR be used to study ATPase binding?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable functional dissection of ATPase binding [5,7].
What is the V-ATPase E subunit?
It is a subunit of the V-ATPase that binds to Cry2Ab toxin in Helicoverpa armigera, mediating toxicity.
How does ATP7B bind copper?
ATP7B has metal-binding domains that interact with copper, influencing its transport function.
What is the PARIS defence system?
A bacterial defence system that relies on ATPase binding for activation against phage infection.
What services does EDITGENE offer for ATPase binding research?
EDITGENE provides CRISPR knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services [1,2,5].
Conclusion
ATPase binding (GO:0051117) is a fundamental molecular function that regulates diverse ATPase-dependent processes, from metal homeostasis to protein degradation. Its dysregulation contributes to diseases such as Wilson disease and cancer. Leveraging CRISPR-based models and EDITGENE's services can accelerate the discovery of novel ATPase binding mechanisms and therapeutic targets.
References
- 1. Zhao Y et al.. 2024. V-ATPase E mediates Cry2Ab binding and toxicity in Helicoverpa armigera.. Pestic Biochem Physiol 198:105744 PMID: 38225087
- 2. DiDonato M et al.. 1999. Expression, purification, and metal binding characteristics of the putative copper binding domain from the Wilson disease copper transporting ATPase (ATP7B).. Adv Exp Med Biol 448:165-73 PMID: 10079824
- 3. Rosen BP et al.. 1999. Mechanism of the ArsA ATPase.. Biochim Biophys Acta 1461(2):207-15 PMID: 10581357
- 4. Penefsky HS. 1979. Mitochondrial ATPase.. Adv Enzymol Relat Areas Mol Biol 49:223-80 PMID: 162556
- 5. Kim YC et al.. 2015. ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function.. Nat Commun 6:8520 PMID: 26465836
- 6. Håkansson KO. 2009. The structure of Mg-ATPase nucleotide-binding domain at 1.6 A resolution reveals a unique ATP-binding motif.. Acta Crystallogr D Biol Crystallogr 65(Pt 11):1181-6 PMID: 19923713
- 7. Deep A et al.. 2024. Architecture and activation mechanism of the bacterial PARIS defence system.. Nature 634(8033):432-439 PMID: 39112702
- 8. Mandal AK et al.. 2003. Functional roles of metal binding domains of the Archaeoglobus fulgidus Cu(+)-ATPase CopA.. Biochemistry 42(37):11040-7 PMID: 12974640
