{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Choi T"],"funding":["NEI NIH HHS"],"pagination":["14990"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10573802"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(19)"],"pubmed_abstract":["Lumican is an extracellular matrix proteoglycan known to regulate toll-like receptor (TLR) signaling in innate immune cells. In experimental settings, lumican suppresses TLR9 signaling by binding to and sequestering its synthetic ligand, CpG-DNA, in non-signal permissive endosomes. However, the molecular details of lumican interactions with CpG-DNA are obscure. Here, the 3-D structure of the 22 base-long CpG-DNA (CpG ODN_2395) bound to lumican or TLR9 were modeled using homology modeling and docking methods. Some of the TLR9-CpG ODN_2395 features predicted by our model are consistent with the previously reported TLR9-CpG DNA crystal structure, substantiating our current analysis. Our modeling indicated a smaller buried surface area for lumican-CpG ODN_2395 (1803 Å<sup>2</sup>) compared to that of TLR9-CpG ODN_2395 (2094 Å<sup>2</sup>), implying a potentially lower binding strength for lumican and CpG-DNA than TLR9 and CpG-DNA. The docking analysis identified 32 amino acids in lumican LRR1-11 interacting with CpG ODN_2395, primarily through hydrogen bonding, salt-bridges, and hydrophobic interactions. Our study provides molecular insights into lumican and CpG-DNA interactions that may lead to molecular targets for modulating TLR9-mediated inflammation and autoimmunity."],"journal":["International journal of molecular sciences"],"pubmed_title":["Three-Dimensional Modeling of CpG DNA Binding with Matrix Lumican Shows Leucine-Rich Repeat Motif Involvement as in TLR9-CpG DNA Interactions."],"pmcid":["PMC10573802"],"funding_grant_id":["R01 EY026104","R01EY026104(S.C)","R01 EY030917","R01EY030917 (S.C)"],"pubmed_authors":["Choi T","Maiti G","Chakravarti S"],"additional_accession":[]},"is_claimable":false,"name":"Three-Dimensional Modeling of CpG DNA Binding with Matrix Lumican Shows Leucine-Rich Repeat Motif Involvement as in TLR9-CpG DNA Interactions.","description":"Lumican is an extracellular matrix proteoglycan known to regulate toll-like receptor (TLR) signaling in innate immune cells. In experimental settings, lumican suppresses TLR9 signaling by binding to and sequestering its synthetic ligand, CpG-DNA, in non-signal permissive endosomes. However, the molecular details of lumican interactions with CpG-DNA are obscure. Here, the 3-D structure of the 22 base-long CpG-DNA (CpG ODN_2395) bound to lumican or TLR9 were modeled using homology modeling and docking methods. Some of the TLR9-CpG ODN_2395 features predicted by our model are consistent with the previously reported TLR9-CpG DNA crystal structure, substantiating our current analysis. Our modeling indicated a smaller buried surface area for lumican-CpG ODN_2395 (1803 Å<sup>2</sup>) compared to that of TLR9-CpG ODN_2395 (2094 Å<sup>2</sup>), implying a potentially lower binding strength for lumican and CpG-DNA than TLR9 and CpG-DNA. The docking analysis identified 32 amino acids in lumican LRR1-11 interacting with CpG ODN_2395, primarily through hydrogen bonding, salt-bridges, and hydrophobic interactions. Our study provides molecular insights into lumican and CpG-DNA interactions that may lead to molecular targets for modulating TLR9-mediated inflammation and autoimmunity.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Oct","modification":"2024-11-19T16:04:34.114Z","creation":"2024-11-19T16:04:34.114Z"},"accession":"S-EPMC10573802","cross_references":{"pubmed":["37834438"],"doi":["10.3390/ijms241914990"]}}