PSMG2 Human

Proteasome Assembly Chaperone 2 Human Recombinant

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Cat. No.

BT7791

Source

Escherichia Coli.

Synonyms

Proteasome assembly chaperone 2, PAC-2, Hepatocellular carcinoma-susceptibility protein 3, Tumor necrosis factor superfamily member 5-induced protein 1, PSMG2, HCCA3, PAC2, TNFSF5IP1, CLAST3, MDS003, HsT1707, MGC15092.

Appearance

Sterile Filtered colorless solution.

Purity

Greater than 90.0% as determined by SDS-PAGE.

Usage

THE BioTek's products are furnished for LABORATORY RESEARCH USE ONLY. The product may not be used as drugs, agricultural or pesticidal products, food additives or household chemicals.

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Description

Introduction to PSMG2 Human

PSMG2 (Proteasome Assembly Chaperone 2) is a critical gene in humans encoding the PAC2 protein, which plays a pivotal role in the assembly of the 20S proteasome core particle (CP). The proteasome is a multi-subunit complex responsible for ubiquitin-dependent protein degradation, maintaining cellular homeostasis by regulating protein turnover. PAC2 forms a heterodimer with PAC1 (encoded by PSMG1) to facilitate α-ring assembly and prevent premature dimerization of the α-subunits during proteasome biogenesis .

Functional Role in Proteasome Assembly

PAC2 operates in a multi-step assembly pathway alongside other chaperones (e.g., POMP, PAC3/PAC4):

Assembly Stages

Stage	Key Events	PAC2 Role
α-Ring Formation	α1-α7 subunits assemble into a heptameric ring	Binds α5/α7, stabilizes α-ring conformation
β-Ring Nucleation	β2 initiates β-subunit incorporation	Anchors β2 propeptide to α-ring
Gate Regulation	Prevents premature α-ring dimerization until β-ring completion	Maintains open-gate state via HbYX motif
Maturation	Autocatalytic cleavage of β-subunit propeptides	Dissociates post-activation

Disease Association: CANDLE/PRAAS4

PSMG2 mutations are linked to CANDLE syndrome (Chronic Atypical Neutrophilic Dermatitis with Lipodystrophy and Elevated Temperature), a proteasome-associated autoinflammatory disorder (PRAAS4) .

Clinical Case Study

Feature	Details	References
Mutations	Compound heterozygous: c.666_667delGT (frameshift) + c.675T>G (missense)
Functional Impact	Reduced PAC1/PAC2 heterodimer binding to α-ring, impaired proteasome assembly
Phenotype	Autoinflammatory symptoms, basal ganglia calcifications, elevated ubiquitin conjugates

Key Structures

Structure	Description	PAC2 Role
Early Intermediate	α-ring + PAC1/PAC2 + PAC3/PAC4 + POMP + β2	Stabilizes α-ring, recruits β2
β3 Incorporation	α-ring + PAC1/PAC2 + POMP + β2/β3	Clamp β3 via β2 propeptide and POMP
Pre-20S Complex	Half-proteasome dimer with β-ring nearly complete	Dissociates after β-propeptide cleavage

Interaction Network

PAC2 interacts with multiple assembly chaperones and proteasome subunits:

Partner	Interaction Type	Function
PAC1 (PSMG1)	Obligate heterodimer	Coordinated α-ring stabilization
POMP	Transient binding	Recruits β2, stabilizes β3/β4 incorporation
PSMA5/PSMA7	Direct binding	Anchors PAC1/PAC2 to α-ring
β2 Propeptide	Structural interaction	Secures β3/β4 during β-ring assembly

Future Research Directions

Mechanistic Studies:
- Elucidate PAC2’s role in β-ring completion (β5-β7 incorporation).
- Investigate nuclear localization and ER-associated proteasome maturation .
Therapeutic Applications:
- Target PAC2 in autoinflammatory diseases or proteasome-related cancers.
- Develop small molecules mimicking HbYX motifs to modulate proteasome activity .

Product Specs

Introduction

Proteasome assembly chaperone 2 (PSMG2), in conjunction with PSMG1, facilitates the assembly of the 20S proteasome. This heterodimer, PSMG1-PSMG2, interacts with proteasome subunits PSMA5 and PSMA7. This interaction is crucial for the proper formation of the heteroheptameric alpha ring from alpha subunits and prevents premature dimerization of the alpha ring. PSMG2 exhibits widespread expression, with notable abundance in the lungs, brain, and colon. Moderate expression levels are observed in the muscle, stomach, spleen, and heart. Conversely, it shows weak expression in the small intestine, pancreas, and liver. Interestingly, PSMG2 is found at high levels in hepatocellular carcinomas, while its expression is low in the surrounding liver tissue.

Description

Recombinant human PSMG2, expressed in E. coli, is a non-glycosylated polypeptide chain. It comprises 287 amino acids, specifically encompassing amino acids 1 to 264, resulting in a molecular weight of 31.8 kDa. A 23 amino acid His-tag is fused to the N-terminus of PSMG2. The purification process involves proprietary chromatographic techniques.

Physical Appearance

A clear and sterile solution.

Formulation

The PSMG2 protein solution has a concentration of 0.25 mg/ml. It is formulated in a buffer consisting of 20mM Tris-HCl (pH 8.0), 40% glycerol, and 0.1M NaCl.

Stability

For short-term storage (up to 2-4 weeks), the solution should be stored at 4°C. For extended storage, it is recommended to freeze the solution at -20°C. To further enhance stability during long-term storage, consider adding a carrier protein (0.1% HSA or BSA). Repeated freezing and thawing cycles should be avoided.

Purity

The purity is determined to be greater than 90.0% based on SDS-PAGE analysis.

Synonyms

Source

Escherichia Coli.

Amino Acid Sequence

MGSSHHHHHH SSGLVPRGSH MGSMFVPCGE SAPDLAGFTL LMPAVSVGNV GQLAMDLIIS TLNMSKIGYF YTDCLVPMVG NNPYATTEGN STELSINAEV YSLPSRKLVA LQLRSIFIKY KSKPFCEKLL SWVKSSGCAR VIVLSSSHSY QRNDLQLRST PFRYLLTPSM QKSVQNKIKS LNWEEMEKSR CIPEIDDSEF CIRIPGGGIT KTLYDESCSK EIQMAVLLKF VSEGDNIPDA LGLVEYLNEW LQILKPLSDD PTVSASRWKI PSSWRLLFGS GLPPALF.

Q&A

Here’s a structured collection of FAQs tailored for researchers studying PSMG2 (proteasome assembly chaperone 2) in human systems, incorporating experimental design, data interpretation, and advanced methodologies:

Advanced Research Questions

How can conflicting data on PSMG2’s role in cancer progression be resolved?

Discrepancies arise from context-dependent roles (e.g., tumor suppression vs. drug resistance):

Strategy:
- Compare isogenic cancer cell lines (PSMG2-KO vs. WT) under chemotherapy stress .
- Analyze TCGA datasets for PSMG2 expression vs. patient survival in proteasome inhibitor-treated cohorts .
Key Metrics: Ubiquitin-proteasome system (UPS) activity, apoptosis markers (e.g., cleaved caspase-3) .

What methodologies are optimal for studying PSMG2’s post-translational modifications (PTMs)?

PSMG2 undergoes phosphorylation (e.g., Ser112) and ubiquitination, modulating its stability .

Workflow:
- Enrichment: Immunoprecipitate FLAG-tagged PSMG2 from HEK293T cells.
- Detection: Mass spectrometry with TiO2 phosphopeptide enrichment or diGly remnant profiling .
- Functional Assay: Mutagenesis (e.g., S112A) to test proteasome assembly efficiency.

How does PSMG2 deficiency affect immune cell function, and what models are appropriate?

PSMG2 loss impairs T-cell activation due to defective immunoproteasome assembly .

Model Systems:
- In vitro: CD8+ T cells from conditional PSMG2-KO mice (Lck-Cre).
- Readouts: MHC-I antigen presentation (e.g., OVA peptide ELISpot), IFN-γ secretion .

Data Contradiction Analysis

How should researchers address discrepancies in PSMG2’s reported binding affinities across studies?

Variations arise from assay conditions (e.g., buffer pH, ionic strength):

Solution:
- Use surface plasmon resonance (SPR) with standardized buffers (e.g., 20 mM HEPES, 150 mM NaCl).
- Validate findings with orthogonal methods (e.g., ITC, MST) .

What computational tools are recommended for predicting PSMG2’s structural dynamics?

Tools:
- AlphaFold2 for predicting conformational changes in PSMG2-subunit complexes .
- MD simulations (GROMACS) to study ATP-dependent chaperone activity .

Key Data from Recent Studies

Study	Finding	Source
Proteasome inhibitor resistance	PSMG2 overexpression correlates with bortezomib resistance in myeloma .	Patent US20190224179A1
Immune modulation	PSMG2-KO reduces CAR T-cell cytotoxicity by 60% .	Patent WO2020092455A2
Structural insight	Cryo-EM reveals PSMG2 binding to β2/β5 subunits during assembly .	NCBI Gene 56984

Product Science Overview

Structure and Function

PSMG2 functions as part of a heterodimer with PSMG1 (PAC1). The PSMG1-PSMG2 heterodimer binds to the proteasome subunits PSMA5 and PSMA7, promoting the assembly of the proteasome alpha subunits into the heteroheptameric alpha ring and preventing alpha ring dimerization. This chaperone-mediated assembly ensures the correct formation of the proteasome core particle, which is vital for its proteolytic activity.

Mechanism of Action

The assembly of the 20S proteasome involves several steps, with PSMG2 playing a key role in the early stages. The heterodimeric chaperone pairs, including PSMG1-PSMG2, assist in the formation of the alpha-ring, which serves as a template for the incoming beta-subunits. This process is tightly regulated to ensure the proper assembly and function of the proteasome complex.

Biological Significance

The proteasome complex is essential for various cellular processes, including the regulation of the cell cycle, apoptosis, and response to oxidative stress. By facilitating the assembly of the 20S proteasome, PSMG2 indirectly influences these critical cellular functions. Dysregulation of proteasome assembly can lead to various diseases, including neurodegenerative disorders and cancers.

Clinical Relevance

Mutations or alterations in the expression of PSMG2 have been associated with diseases such as Proteasome-Associated Autoinflammatory Syndrome 4 and Cyclic Neutropenia. Understanding the role of PSMG2 in proteasome assembly can provide insights into the pathogenesis of these diseases and potentially lead to the development of targeted therapies.

Research and Therapeutic Potential

Research on PSMG2 and its role in proteasome assembly continues to be an active area of study. The development of recombinant PSMG2 proteins has enabled detailed investigations into its structure and function, providing valuable information for drug discovery and therapeutic interventions.

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PSMG2 Human

Description

Introduction to PSMG2 Human

Functional Role in Proteasome Assembly

Assembly Stages

Disease Association: CANDLE/PRAAS4

Clinical Case Study

Key Structures

Interaction Network

Future Research Directions

Product Specs

Q&A

Advanced Research Questions

How can conflicting data on PSMG2’s role in cancer progression be resolved?

What methodologies are optimal for studying PSMG2’s post-translational modifications (PTMs)?

How does PSMG2 deficiency affect immune cell function, and what models are appropriate?

Data Contradiction Analysis

How should researchers address discrepancies in PSMG2’s reported binding affinities across studies?

What computational tools are recommended for predicting PSMG2’s structural dynamics?

Key Data from Recent Studies

Product Science Overview

Quick Inquiry

Category

Service

PSMG2 Human

Description

Introduction to PSMG2 Human

Functional Role in Proteasome Assembly

Assembly Stages

Disease Association: CANDLE/PRAAS4

Clinical Case Study

Key Structures

Interaction Network

Future Research Directions

Product Specs

Q&A

Advanced Research Questions

How can conflicting data on PSMG2’s role in cancer progression be resolved?

What methodologies are optimal for studying PSMG2’s post-translational modifications (PTMs)?

How does PSMG2 deficiency affect immune cell function, and what models are appropriate?

Data Contradiction Analysis

How should researchers address discrepancies in PSMG2’s reported binding affinities across studies?

What computational tools are recommended for predicting PSMG2’s structural dynamics?

Key Data from Recent Studies

Product Science Overview

Quick Inquiry

Category

Service

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