A 20 Residues Motif Delineates the Furin Cleavage Site and its Physical Properties May Influence Viral Fusion

摘要: Furin is a proprotein convertase that proteolytically cleaves protein precursors to yield functional proteins. Efficient cleavage depends on the presence of specific sequence motif substrate. Currently, site described as four amino acid pattern: R-X-[K/R]-R↓. However, not all furin recognition sites can be by this pattern and R-X-[K/R]-R↓ are cleaved furin. Since many substrates involved in pathogenesis viral infection human diseases, it important accurately characterize motif. In study, was characterized using statistical analysis. The data were interpreted within 3D crystal structure catalytic domain. results indicate comprised about 20 residues, P14–P6´. Specific physical properties such volume, charge, hydrophilicity required at positions. divided into two parts: 1) one core region (8 acids, positions P6–P2´) packed inside binding pocket; 2) polar regions P7–P14; 4 P3´–P6´) located outside pocket. contribute strength substrate, while provide solvent accessible environment facilitate accessibility This also revealed dynamic relationship linking evolution P1´–P6´ fusion peptides, efficacy, infectivity.