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 α-helixes. The extracellular domains of transforming growth factor-β1 receptor I (TβRI-ED) and II (TβRII-ED) were docked with nVAP, respectively. The results show that both of TβR-EDs have high affinity with nVAP which locates near the active center of TβRII-ED integrating with transforming growth factor-β1 (TGF-β1). Otherwise, nVAP can also insert near the "pre-helix extension" of TβRI-ED, which is the key domain to interact on TGF-β1 and TβRII-ED. With the perturbation of nVAP, TβRI-ED can not be recruited by TGF-β1:TβRII-ED complex rigorously. The intracellular domain of TβRI (TβRI-ID) is not phosphorylated and activated by TβRII. This study shows that nVAP prefers tethering TβRI-ED which is more crucial in TGF-β1:TβRII-ED:TβRI-ED complex. Thus nVAP can disturb the TGF-β1 binding pattern by interacting on TβRs (TβRI and TβRII), further intercepting TGF-β1 pathway downstream.