Natural velvet antler polypeptide conformation prediction and molecular docking study with TGF-β1 complex

Based on the chain A structures of hemoglobin (PDB code: 1HDS, 1IBE, 1FAW, 3AT5), the three dimensional (3D) structure of natural velvet antler polypeptide (nVAP) was constructed by homology modeling and molecular dynamics (MD) method. The structural rationality was further checked by Profile-3D and Procheck, both of which confirmed that the 3D structure of nVAP was reasonable. The modeled structure indicates that the stable conformation of nVAP is composed of two alpha-helixes. The extracellular domains of transforming growth factor-beta 1 receptor I (T beta RI-ED) and II (T beta RII-ED) were docked with nVAP, respectively. The results show that both of T beta R-EDs have high affinity with nVAP which locates near the active center of T beta RII-ED integrating with transforming growth factor-beta 1 (TGF-beta 1). Otherwise, nVAP can also insert near the pre-helix extension of T beta RI-ED, which is the key domain to interact on TGF-beta 1 and T beta RII-ED. With the perturbation of nVAP, T beta RI-ED can not be recruited by TGF-beta 1:T beta RII-ED complex rigorously. The intracellular domain of T beta RI (T beta RI-ID) is not phosphorylated and activated by T beta RII. This study shows that nVAP prefers tethering T beta RI-ED which is more crucial in TGF-beta 1:T beta RII-ED:T beta RI-ED complex. Thus nVAP can disturb the TGF-beta 1 binding pattern by interacting on T beta Rs (T beta RI and T beta RII), further intercepting TGF-beta 1 pathway downstream.