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. 2025 Feb 28;16:1520777. doi: 10.3389/fimmu.2025.1520777

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Copyright © 2025 Leung, Qu, Ye and Zhong

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Visualization of OPN protein isoforms and interactions with integrins. Figure 2 shows examples of OPN protein isoforms binding to two types of integrins. Visual analysis revealed that OPNa, OPNb, and OPNc exhibit similar protein structures, whereas OPN-4 and OPN-5 possess unique protein configurations. The distinctions among the isoforms become more pronounced upon thrombin cleavage. Following thrombin cleavage, the RGD domains of OPNa, OPNb, and OPNc can bind more tightly to integrins, whereas OPN4 and OPN5 demonstrate inadequate binding affinity to integrins, regardless of whether they have undergone thrombin cleavage. (A) The structures of the full-length OPN-a, OPN-b and OPN-c isoforms. OPN-a is displayed in blue, OPN-b is displayed in pink, and OPN-c is displayed in gray. (B) The structure of the full-length OPN-4 isoform. (C) The structure of the full-length OPN-5 isoform. (D) The structures of the thrombin-cleaved OPN-a, OPN-b and OPN-c isoforms. OPN-a is displayed in blue, OPN-b is displayed in pink, and OPN-c is displayed in gray. (E) The structure of the thrombin-cleaved OPN-4 isoform. (F) The structure of the thrombin-cleaved OPN-5 isoform. (G) The binding mode of the FL-OPN-a isoform and integrin-α4. (H) The binding mode of the FL-OPN-b isoform and integrin-α9. (I) The binding mode of the FL-OPN-5 isoform and integrin-α4. (J) The binding mode of the CL-OPN-a isoform and integrin-α4. (K) The binding mode of the CL-OPN-b isoform and integrin-α9. (L) The binding mode of the CL-OPN-5 isoform and integrin-α4. FL-OPN = full-length OPN; CL-OPN = cleaved OPN.