MSH3 Antibodies

Structure of MSH3

MSH3 is a medium-sized protein with a molecular weight of approximately 110 kDa. This protein is encoded by the 5q14 region of the human chromosome and contains 1,137 amino acid residues. It has highly conserved sequence characteristics in different mammals.

The core structure of the MSH3 protein consists of the N-terminal mismatch recognition domain, the central ATPase domain, and the C-terminal dimerization interface. Its mismatch recognition domain forms a unique clamp conformation and interacts with the DNA skeleton through positively charged amino acid residues. The ATPase domain adopts the classic Walker A/B motif, and conformational changes are driven by the ATP-binding hydrolysis cycle. The C-terminal helical structure mediates the stable binding to the MSH2 subunit, jointly forming the functional MutSβ complex. This highly ordered multi-domain structure enables it to specifically recognize insertion/deletion loops of 1 to 16 nucleotides and play a molecular switch role in the process of DNA damage repair.

Fig. 1 Structural and sequence analysis of MSH3.¹

Key structural properties of MSH3:

• Contains a classic ATP dual module combined with domain and mismatch recognition domain
• Form a clamp-like dimer interface to synergistically bind DNA
• Specific helix-turn-helix motifs are responsible for recognizing DNA insertion/deletion loops

Functions of MSH3

The core function of the MSH3 gene is to participate in DNA mismatch repair. However, this gene also plays a significant role in various cellular processes, including gene recombination regulation and cell cycle checkpoint responses.

The MutSβ complex formed by MSH3 and MSH2 demonstrates substrate specificity distinct from other mismatch repair proteins. Its functional loss mainly leads to insertion/deletion instability of microsatellite sequences rather than single nucleotide variations, which reflects its unique role in maintaining stability in specific genomic regions.

Applications of MSH3 and MSH3 Antibody in Literature

1. O'Reilly, Daniel, et al. "Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington's disease." Molecular Therapy 31.6 (2023): 1661-1674. https://doi.org/10.1016/j.ymthe.2023.05.006

This study found that a chemically modified siRNA can effectively silence the MSH3 gene, thereby blocking the somatic expansion of CAG repeat sequences in the Huntington's disease mouse model without affecting other functions of the mismatch repair system, providing a new strategy for the treatment of this type of disease.

2. Oh, Jung-Min, et al. "MSH2-MSH3 promotes DNA end resection during homologous recombination and blocks polymerase theta-mediated end-joining through interaction with SMARCAD1 and EXO1." Nucleic acids research 51.11 (2023): 5584-5602. https://doi.org/10.1093/nar/gkad308

Research has found that the MSH2-MSH3 complex is recruited to the double-strand breaks of DNA through interaction with SMARCAD1. It guides repair towards homologous recombination rather than error-prone terminal connection pathways by promoting exo1-mediated long-range terminal excision and inhibiting the POLθ pathway.

3. Medina-Rivera, Melisa, et al. "Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo." Nucleic Acids Research 51.22 (2023): 12185-12206. https://doi.org/10.1093/nar/gkad934

Studies have shown that abnormally elevated levels of the MSH2-MSH3 complex can actively interfere with DNA replication and base excision repair through its ATPase activity, and cause cell cycle arrest. This reveals the crucial impact of MSH2-MSH3 protein abundance on its dual role in genomic stability.

4. Aelvoet, Arthur S., et al. "A large family with MSH3-related polyposis." Familial Cancer 22.1 (2023): 49-54. https://doi.org/10.1007/s10689-022-00297-x

Research has found that the biallelic pathogenic variation of the MSH3 gene is a rare cause of attenuated adenomatous polyposis. It was confirmed in a large family that this variation can cause colorectal adenomatous polyposis that occurs in middle age, and the EMAST phenotype was detected in both tumors and normal mucosa.

5. Koi, Minoru, et al. "Compound heterozygous MSH3 germline variants and associated tumor somatic DNA mismatch repair dysfunction." NPJ Precision Oncology 8.1 (2024): 12. https://doi.org/10.1038/s41698-024-00511-2

This study reports the fourth case caused by a biallelic germline variation of the MSH3 gene. The patient was diagnosed with colon cancer in middle age, and the tumor presented EMAST characteristics. Research has found that the mutated MSH3 protein is abnormally located on the cytoplasm and membrane, unable to enter the nucleus, and may induce tumorigenesis by interfering with the formation of the MSH2-MSH6 complex.

Creative Biolabs: MSH3 Antibodies for Research

Creative Biolabs specializes in the production of high-quality MSH3 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom MSH3 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our MSH3 antibodies, custom preparations, or technical support, contact us at email.