GO:1990322 collagen type XXIII trimer: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1990322 describes the collagen type XXIII trimer, a homotrimer of alpha1(XXIII) chains that forms a triple helix spanning the plasma membrane.
• Type XXIII collagen belongs to the MACIT (membrane-associated collagens with interrupted triple helices) family, which is conserved from bilaterians to humans.
• The trimer is stabilized by disulfide bonds and alpha-helical coiled-coil motifs that direct oligomerization.
• MACITs, including type XXIII collagen, function in cell adhesion, migration, and tissue remodeling, and are implicated in cancer progression.
• Studying this trimer requires methods such as knockout, knock-in, and overexpression models to dissect its role in membrane biology.
• EDITGENE provides CRISPR services to generate precise cell models for functional studies of collagen type XXIII trimer and related MACITs.
Description
The collagen type XXIII trimer (GO:1990322) is a cellular component defined as a homotrimer of alpha1(XXIII) chains, where the type XXIII collagen triple helices span the plasma membrane. This structure is part of the membrane-associated collagens with interrupted triple helices (MACITs), a unique subgroup of collagens that are integral membrane proteins rather than secreted extracellular matrix components. Understanding this trimer is essential because it represents a direct link between the extracellular environment and intracellular signaling, influencing cell behavior in development and disease. Researchers are interested in GO:1990322 because it provides a precise ontological handle for studying membrane-bound collagen assemblies. The trimer's topology, with triple-helical domains on both sides of the membrane, suggests roles in cell adhesion and receptor-like functions. Moreover, the conservation of MACITs across bilaterians highlights their fundamental biological importance. Despite its significance, the collagen type XXIII trimer remains understudied compared to fibrillar collagens. This article synthesizes current knowledge from QuickGO and PubMed to outline its definition, assembly, molecular mechanisms, and research approaches, enabling targeted investigations.
collagen type XXIII trimer At A Glance
| GO ID | GO:1990322 |
|---|---|
| GO term | collagen type XXIII trimer |
| Ontology | cellular_component |
| Synonym | None |
| Major function | Transmembrane collagen homotrimer involved in cell adhesion and membrane organization |
| Definition | A collagen homotrimer of alpha1(XXIII) chains; type XXIII collagen triple helices span the plasma membrane |
| Family | MACIT (membrane-associated collagens with interrupted triple helices) |
| Conservation | Evolved from a bilaterian common ancestor; functional conservation in C. elegans |
What Is GO:1990322?
GO:1990322, collagen type XXIII trimer, is a protein complex located in the plasma membrane. It consists of three identical alpha1(XXIII) collagen chains that assemble into a triple-helical structure. Unlike typical collagens that form extracellular fibrils, this trimer is a transmembrane protein, with its triple-helical domains interrupted by non-collagenous regions, allowing it to span the lipid bilayer. The term is classified under the cellular component ontology, reflecting its role as a structural element of the cell membrane.
Why Is collagen type XXIII trimer Important in Cell Biology?
The collagen type XXIII trimer is important because it exemplifies a non-canonical collagen function as a membrane-spanning protein, bridging cell-extracellular matrix interactions with intracellular signaling. Its unique structure, stabilized by coiled-coil and disulfide bonds, provides a model for studying membrane protein assembly. Dysregulation of MACITs has been linked to cancer and tissue remodeling, making this trimer a potential therapeutic target. Furthermore, its evolutionary conservation underscores its fundamental role in metazoan biology.
• Provides a structural link between the plasma membrane and extracellular matrix, influencing cell adhesion and migration.
• Serves as a model for understanding transmembrane collagen assembly and oligomerization.
• Implicated in cancer progression and tissue remodeling, offering a target for therapeutic intervention.
• Conserved across bilaterians, enabling functional studies in model organisms like C. elegans.
• Its unique triple-helical transmembrane topology challenges conventional views of collagen function.
• Disulfide bonds and coiled-coil motifs are critical for its biosynthesis and stability.
• Knockout and knock-in models can elucidate its role in development and disease.
• Potential biomarker for diseases involving membrane collagen dysfunction.
• Research on this trimer may reveal new mechanisms of cell signaling.
• Understanding its regulation could lead to novel CRISPR-based therapies.
Structure and Composition of collagen type XXIII trimer
Alpha1(XXIII) Chain Structure
In simple terms: The trimer is made of three identical protein chains that each weave through the cell membrane.
The collagen type XXIII trimer is a homotrimer composed of three alpha1(XXIII) chains. Each chain contains a long triple-helical domain interrupted by non-collagenous regions, allowing the trimer to span the plasma membrane. The alpha1(XXIII) chain is encoded by the COL23A1 gene and belongs to the MACIT family.
Coiled-Coil Motifs and Oligomerization
In simple terms: Special spiral-shaped regions in the chains help them stick together to form the trimer.
Type XXIII collagen contains two separate coiled-coil motifs that may function as independent oligomerization domains. These motifs are crucial for the assembly of the triple helix and are conserved among transmembrane collagens. The coiled-coil domains facilitate the initial association of the three alpha1(XXIII) chains before triple-helix formation.
Disulfide Bond Stabilization
In simple terms: Chemical bridges called disulfide bonds lock the three chains together, making the trimer stable.
Disulfide bonds play a key role in the biosynthesis and stability of type XXIII collagen and other collagenous transmembrane proteins. These covalent linkages form between cysteine residues in the non-collagenous domains, ensuring proper folding and assembly of the trimer.
Membrane Spanning Topology
In simple terms: The trimer crosses the cell membrane, with parts inside and outside the cell.
The triple-helical domains of type XXIII collagen span the plasma membrane, a unique feature among collagens. This topology allows the trimer to interact with both extracellular matrix components and intracellular proteins, potentially mediating signal transduction.
Evolutionary Conservation
In simple terms: This trimer has been around since ancient animals and is found in many species.
MACITs, including type XXIII collagen, evolved from a bilaterian common ancestor and show functional conservation in C. elegans. This evolutionary persistence highlights the fundamental role of the collagen type XXIII trimer in metazoan biology.
Key Genes Involved in GO:1990322 collagen type XXIII trimer
The following genes and proteins are directly involved in the structure, assembly, and function of the collagen type XXIII trimer.
| Gene | Major Role | Research Relevance |
|---|---|---|
| COL23A1 | Encodes the alpha1(XXIII) chain of the trimer | Core component; mutations may affect trimer assembly |
| COL13A1 | Encodes type XIII collagen, a related MACIT | Shares coiled-coil motifs and disulfide bond patterns |
| COL25A1 | Encodes type XXV collagen, another MACIT | Comparative studies of transmembrane collagens |
| COL4A1 | Encodes type IV collagen, a basement membrane collagen | Contrasts with transmembrane collagens |
| HSP47 | Collagen-specific chaperone | Assists in triple-helix folding |
| PDI | Protein disulfide isomerase | Catalyzes disulfide bond formation in collagens |
| Coiled-coil domain proteins | Facilitate oligomerization | Potential regulators of trimer assembly |
| Integrins | Cell adhesion receptors | May interact with the trimer's extracellular domain |
| MMPs | Matrix metalloproteinases | Can cleave membrane collagens, affecting function |
| C. elegans MACIT homologs | Functional conservation | Model for genetic studies |
| COL23A1 splice variants | Alternative isoforms | May regulate trimer diversity |
| Cysteine residues in COL23A1 | Form disulfide bonds | Critical for stability |
| Coiled-coil motifs in COL23A1 | Oligomerization domains | Targets for mutagenesis |
| Plasma membrane lipids | Membrane environment | Influence trimer topology |
| Extracellular matrix proteins | Ligands for trimer | Modulate cell adhesion |
| Intracellular signaling proteins | Interact with cytoplasmic tail | Potential signal transduction |
How Is collagen type XXIII trimer Regulated?
The assembly and function of the collagen type XXIII trimer are regulated at multiple levels. Transcriptional control of COL23A1 determines the availability of alpha1(XXIII) chains. Post-translationally, disulfide bond formation and coiled-coil-mediated oligomerization are critical for trimer stability. Chaperones such as HSP47 assist in triple-helix folding. Additionally, proteolytic cleavage by matrix metalloproteinases can release the ectodomain, modulating its interactions. The membrane environment and interactions with other proteins may also influence trimer function.
collagen type XXIII trimer and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| COL23A1 | Cancer progression | Knockout cancer cell lines |
| COL23A1 | Fibrosis | Overexpression in fibroblasts |
| COL13A1 | Related MACIT disorders | Point mutation models |
| COL25A1 | Alzheimer's disease (related MACIT) | Knock-in mouse models |
| C. elegans MACIT homologs | Developmental defects | CRISPR knockout in C. elegans |
Cancer Progression
MACITs, including type XXIII collagen, have been implicated in cancer progression. Their expression is altered in various tumors, and they may promote cell migration and invasion. The collagen type XXIII trimer's ability to span the membrane suggests it could transmit signals from the tumor microenvironment to cancer cells.
Tissue Remodeling and Fibrosis
Dysregulation of membrane collagens can lead to aberrant tissue remodeling. The collagen type XXIII trimer may contribute to fibrosis by affecting cell-matrix interactions and matrix stiffness.
Developmental Disorders
Given its evolutionary conservation, mutations in COL23A1 could disrupt development. Studies in C. elegans have shown that MACITs are essential for normal morphogenesis.
From collagen type XXIII trimer-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| What is the role of COL23A1 in cell adhesion? | Knockout cell lines |
| How do disulfide bonds affect trimer stability? | Point mutations in cysteine residues |
| Can the trimer be tagged for imaging? | Knock-in with fluorescent tag |
| What is the effect of COL23A1 overexpression? | Overexpression cell lines |
| Which proteins interact with the trimer? | Knock-in with affinity tag for proteomics |
| Is the trimer conserved in invertebrates? | C. elegans knockout models |
How to Study the collagen type XXIII trimer Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Loss of function | Determine role in cell adhesion |
| Point mutation | Specific residue function | Test disulfide bond importance |
| Knock-in tagging | Protein localization | Imaging and proteomics |
| Overexpression | Gain of function | Study effects on migration |
| Immunoprecipitation | Protein interactions | Identify binding partners |
| Mass spectrometry | Proteome-wide changes | Discover signaling pathways |
| Fluorescence microscopy | Subcellular localization | Confirm membrane spanning |
| Cell migration assay | Functional behavior | Assess role in cancer |
CRISPR-Cas9 Genome Editing
CRISPR-Cas9 is used to generate knockout, point mutation, and knock-in models for studying the collagen type XXIII trimer. Knockout of COL23A1 can reveal its role in cell adhesion and migration. Point mutations in cysteine residues can test the importance of disulfide bonds. Knock-in of tags enables visualization and interaction studies.
Proteomics and Interaction Studies
Proteomic approaches such as immunoprecipitation coupled with mass spectrometry can identify proteins interacting with the collagen type XXIII trimer. This helps elucidate its signaling partners and structural components.
Imaging and Localization
Fluorescence microscopy of tagged trimer can reveal its plasma membrane localization and dynamics. Super-resolution imaging can provide insights into its topology and assembly.
Functional Assays
Cell adhesion, migration, and proliferation assays are used to assess the functional consequences of manipulating the collagen type XXIII trimer. These assays help link the trimer to cellular behaviors.
How CRISPR Can Be Used to Study GO:1990322 collagen type XXIII trimer
Knockout
CRISPR knockout of COL23A1 eliminates the alpha1(XXIII) chain, preventing trimer formation. This model is used to study the trimer's role in cell adhesion, migration, and signaling. Knockout cell lines can be validated by western blot and functional assays.
Point Mutation
Point mutations can be introduced into COL23A1 to disrupt specific residues, such as cysteines involved in disulfide bonds or amino acids in coiled-coil domains. These models help dissect the molecular requirements for trimer assembly and stability.
Knock-in
Knock-in of tags (e.g., GFP, HA) into the endogenous COL23A1 locus allows real-time imaging and biochemical isolation of the trimer. This approach preserves native regulation and provides insights into its dynamics.
Overexpression
Overexpression of COL23A1 using lentiviral or plasmid vectors leads to increased trimer levels. This model is useful for gain-of-function studies, such as assessing effects on cell proliferation and matrix remodeling.
How EDITGENE Supports collagen type XXIII trimer Research
Researchers studying collagen type XXIII trimer-related genes often need to determine whether a candidate gene is causally involved in trimer assembly, membrane dynamics, or disease progression. EDITGENE provides a comprehensive suite of CRISPR services to generate precise cell models, enabling rigorous functional studies.
Contact EDITGENE today to design your custom CRISPR model for collagen type XXIII trimer research.
Frequently Asked Questions About collagen type XXIII trimer
What is GO:1990322?
GO:1990322 is the Gene Ontology term for collagen type XXIII trimer, a homotrimer of alpha1(XXIII) chains that spans the plasma membrane.
What genes are involved in collagen type XXIII trimer?
The primary gene is COL23A1, which encodes the alpha1(XXIII) chain. Related MACIT genes include COL13A1 and COL25A1.
Where is collagen type XXIII trimer located?
It is located in the plasma membrane, with triple-helical domains spanning the lipid bilayer.
What is the function of collagen type XXIII trimer?
It is thought to mediate cell adhesion and signaling between the extracellular matrix and intracellular environment.
How is collagen type XXIII trimer assembled?
Three alpha1(XXIII) chains associate via coiled-coil motifs and are stabilized by disulfide bonds to form the triple helix.
Is collagen type XXIII trimer conserved?
Yes, MACITs including type XXIII collagen evolved from a bilaterian common ancestor and are conserved in C. elegans.
What diseases are associated with collagen type XXIII trimer?
It has been implicated in cancer progression and tissue remodeling, though direct evidence is still emerging.
How can I study collagen type XXIII trimer?
CRISPR knockout, point mutation, knock-in, and overexpression models, combined with imaging and proteomics, are key approaches.
What are MACITs?
MACITs are membrane-associated collagens with interrupted triple helices, a family that includes type XXIII collagen.
Does collagen type XXIII trimer have a synonym?
No, QuickGO lists no synonyms for GO:1990322.
Conclusion
The collagen type XXIII trimer (GO:1990322) is a unique transmembrane collagen assembly with roles in cell adhesion, signaling, and disease. Its study requires precise genetic models to dissect its assembly and function. EDITGENE's CRISPR services provide the tools needed to advance this research.
References
- 1. Latvanlehto A et al.. 2003. Type XIII collagen and some other transmembrane collagens contain two separate coiled-coil motifs, which may function as independent oligomerization domains.. J Biol Chem 278(39):37590-9 PMID: 12832406
- 2. Snellman A et al.. 2007. The role of disulfide bonds and alpha-helical coiled-coils in the biosynthesis of type XIII collagen and other collagenous transmembrane proteins.. J Biol Chem 282(20):14898-905 PMID: 17344215
- 3. Tu H et al.. 2015. Membrane-associated collagens with interrupted triple-helices (MACITs): evolution from a bilaterian common ancestor and functional conservation in C. elegans.. BMC Evol Biol 15:281 PMID: 26667623
