Crystal structure of the nonclassical cadherin-17 N-terminus and implications for its adhesive binding mechanism

Gray, Michelle E.; Sotomayor, Marcos

doi:10.1107/s2053230x21002247

Cited by 3 publications

(3 citation statements)

References 87 publications

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“…Lys115 is located on the opposite side of the interface of the EC1-4 homodimer and does not directly contribute to the formation of the homodimer (Figure 3). The architecture of the EC1-2 homodimer expressed in E. coli has been reported previously (23). The authors pointed out that N-glycans bound to EC2 seemed to hamper the homodimer formation.…”

Section: Resultsmentioning

confidence: 71%

Molecular mechanism underlying the increased risk of colorectal cancer metastasis caused by single nucleotide polymorphisms in LI-cadherin gene

Yui

Kuroda

Maruno

et al. 2022

Preprint

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LI-cadherin is a member of the cadherin superfamily. LI-cadherin mediates Ca2+-dependent cell-cell adhesion by forming a homodimer. A previous study reported two single nucleotide polymorphisms (SNPs) in the LI-cadherin-coding gene (CDH17). These SNPs correspond to the amino acid changes of Lys115 to Glu and Glu739 to Ala. Patients with colorectal cancer carrying these SNPs are reported to have a higher risk of lymph node metastasis than patients without the SNPs. Although proteins associated with metastasis have been identified, the molecular mechanisms underlying the functions of these proteins remain unclear, making it difficult to develop effective strategies to prevent metastasis. In this study, we employed biochemical assays and molecular dynamics (MD) simulations to elucidate the molecular mechanisms by which the amino acid changes caused by SNPs in the LI-cadherin-coding gene increase the risk of cancer metastasis. Cell aggregation assays showed that the amino acid changes weakened the LI-cadherin-dependent cell-cell adhesion. In vitro assays demonstrated a decrease in homodimerization tendency due to the mutation of Lys115, and MD simulations suggested an alteration in the intramolecular hydrogen bond network due to the amino acid change. Taken together, our results indicate that the increased risk of lymph node metastasis is due to weakened cell-cell adhesion caused by the decrease in homodimerization tendency.

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Section: Resultsmentioning

confidence: 71%

Molecular mechanism underlying the increased risk of colorectal cancer metastasis caused by single nucleotide polymorphisms in LI-cadherin gene

Yui

Kuroda

Maruno

et al. 2022

Preprint

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“…3). The architecture of the EC1-2 homodimer expressed in E. coli has been reported previously 23 . The authors pointed out that N-glycans bound to EC2 seemed to hamper the homodimer formation.…”

Section: Effect Of Amino Acid Changes On Li-cadherin-dependent Cell-c...mentioning

confidence: 87%

Molecular mechanism underlying the increased risk of colorectal cancer metastasis caused by single nucleotide polymorphisms in LI-cadherin gene

Yui

Kuroda

Maruno

et al. 2023

Sci Rep

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LI-cadherin is a member of the cadherin superfamily. LI-cadherin mediates Ca2+-dependent cell–cell adhesion through homodimerization. A previous study reported two single nucleotide polymorphisms (SNPs) in the LI-cadherin-coding gene (CDH17). These SNPs correspond to the amino acid changes of Lys115 to Glu and Glu739 to Ala. Patients with colorectal cancer carrying these SNPs are reported to have a higher risk of lymph node metastasis than patients without the SNPs. Although proteins associated with metastasis have been identified, the molecular mechanisms underlying the functions of these proteins remain unclear, making it difficult to develop effective strategies to prevent metastasis. In this study, we employed biochemical assays and molecular dynamics (MD) simulations to elucidate the molecular mechanisms by which the amino acid changes caused by the SNPs in the LI-cadherin-coding gene increase the risk of metastasis. Cell aggregation assays showed that the amino acid changes weakened the LI-cadherin-dependent cell–cell adhesion. In vitro assays demonstrated a decrease in homodimerization tendency and MD simulations suggested an alteration in the intramolecular hydrogen bond network by the mutation of Lys115. Taken together, our results indicate that the increased risk of lymph node metastasis is due to weakened cell–cell adhesion caused by the decrease in homodimerization tendency.

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“…The histological equivalents of these connections are called adherens junctions (AJs) and are indispensable for epithelial integrity and barrier functions. Similar to FAs, AJs are intracellularly coupled to further signal-transducing proteins comprising members of the catenin family and the actin cytoskeleton [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues

et al. 2021

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Among oral tissues, the periodontium is permanently subjected to mechanical forces resulting from chewing, mastication, or orthodontic appliances. Molecularly, these movements induce a series of subsequent signaling processes, which are embedded in the biological concept of cellular mechanotransduction (MT). Cell and tissue structures, ranging from the extracellular matrix (ECM) to the plasma membrane, the cytosol and the nucleus, are involved in MT. Dysregulation of the diverse, fine-tuned interaction of molecular players responsible for transmitting biophysical environmental information into the cell’s inner milieu can lead to and promote serious diseases, such as periodontitis or oral squamous cell carcinoma (OSCC). Therefore, periodontal integrity and regeneration is highly dependent on the proper integration and regulation of mechanobiological signals in the context of cell behavior. Recent experimental findings have increased the understanding of classical cellular mechanosensing mechanisms by both integrating exogenic factors such as bacterial gingipain proteases and newly discovered cell-inherent functions of mechanoresponsive co-transcriptional regulators such as the Yes-associated protein 1 (YAP1) or the nuclear cytoskeleton. Regarding periodontal MT research, this review offers insights into the current trends and open aspects. Concerning oral regenerative medicine or weakening of periodontal tissue diseases, perspectives on future applications of mechanobiological principles are discussed.

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Crystal structure of the nonclassical cadherin-17 N-terminus and implications for its adhesive binding mechanism

Cited by 3 publications

References 87 publications

Molecular mechanism underlying the increased risk of colorectal cancer metastasis caused by single nucleotide polymorphisms in LI-cadherin gene

Molecular mechanism underlying the increased risk of colorectal cancer metastasis caused by single nucleotide polymorphisms in LI-cadherin gene

Molecular mechanism underlying the increased risk of colorectal cancer metastasis caused by single nucleotide polymorphisms in LI-cadherin gene

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues

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