%0 Journal Article %T A 20 Residues Motif Delineates the Furin Cleavage Site and its Physical Properties May Influence Viral Fusion %A Sun Tian %J Biochemistry Insights %D 2012 %I %X Furin is a proprotein convertase that proteolytically cleaves protein precursors to yield functional proteins. Efficient cleavage depends on the presence of a specific sequence motif on the substrate. Currently, the cleavage site motif is described as a four amino acid pattern: R-X-[K/R]-R∣. However, not all furin cleavage recognition sites can be described by this pattern and not all R-X-[K/R]-R∣ sites are cleaved by furin. Since many furin substrates are involved in the pathogenesis of viral infection and human diseases, it is important to accurately characterize the furin cleavage site motif. In this study, the furin cleavage site motif was characterized using statistical analysis. The data were interpreted within the 3D crystal structure of the furin catalytic domain. The results indicate that the furin cleavage site motif is comprised of about 20 residues, P14每P6∩. Specific physical properties such as volume, charge, and hydrophilicity are required at specific positions. The furin cleavage site motif is divided into two parts: 1) one core region (8 amino acids, positions P6每P2∩) packed inside the furin binding pocket; 2) two polar regions (8 amino acids, positions P7每P14; and 4 amino acids, positions P3∩每P6∩) located outside the furin binding pocket. The physical properties of the core region contribute to the binding strength of the furin substrate, while the polar regions provide a solvent accessible environment and facilitate the accessibility of the core region to the furin binding pocket. This furin cleavage site motif also revealed a dynamic relationship linking the evolution of physical properties in region P1∩每P6∩ of viral fusion peptides, furin cleavage efficacy, and viral infectivity. %U http://www.la-press.com/a-20-residues-motif-delineates-the-furin-cleavage-site-and-its-physica-article-a1407