TAILIEUCHUNG - Báo cáo khoa học: Binding areas of urokinase-type plasminogen activator– plasminogen activator inhibitor-1 complex for endocytosis receptors of the low-density lipoprotein receptor family, determined by site-directed mutagenesis

Some endocytosis receptors related to the low-density lipoprotein receptor, including low-density lipoprotein receptor-related protein-1A, very-low-density lipoprotein receptor, and sorting protein-related receptor, bind pro-tease-inhibitor complexes, including urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and the uPA–PAI-1 com-plex. | ỊFEBS Journal Binding areas of urokinase-type plasminogen activatorplasminogen activator inhibitor-1 complex for endocytosis receptors of the low-density lipoprotein receptor family determined by site-directed mutagenesis Ixzt I I o 11 I a lz kt I u re o n1 ri n o F Porlorcon1 I I zt 11 zt I I D zt zt ronn 1 D ilflsa F iol I I n d 1 oune SkulUal JalkUU V. Lalocll Katrine E. rcUclocll Helle H. rctclocll Rikke cgeiuild Anni Christensen1 Jan K. Jensen1 2 J0rgen Gliemann3 and Peter A. Andreasen1 2 1 Department of Molecular Biology University of Aarhus Denmark 2 Interdisciplinary Nanoscience Center iNANO University of Aarhus Denmark 3 Department of MedicalBiochemistry University of Aarhus Denmark Keywords low-density lipoprotein receptor-related protein plasminogen activator inhibitor 1 sorting protein-related receptor urokinase plasminogen activator very-low-density lipoprotein receptor Correspondence P. A. Andreasen Department of Molecular Biology University of Aarhus Gustav Wied s Vej10C 8000 Aarhus C Denmark Fax 45 86 12 31 78 Tel 45 89 42 50 80 E-mail pa@ Received 17 July 2006 revised 20 September 2006 accepted 22 September 2006 doi Some endocytosis receptors related to the low-density lipoprotein receptor including low-density lipoprotein receptor-related protein-lA very-low-density lipoprotein receptor and sorting protein-related receptor bind protease-inhibitor complexes including urokinase-type plasminogen activator uPA plasminogen activator inhibitor-1 PAI-1 and the uPA-PAI-1 complex. The unique capacity of these receptors for high-affinity binding of many structurally unrelated ligands renders mapping of receptor-binding surfaces of serpin and serine protease ligands a special challenge. We have mapped the receptor-binding area of the uPA-PAI-1 complex by site-directed mutagenesis. Substitution of a cluster of basic residues near the 37-loop and 60-loop of uPA reduced the receptor-binding affinity of the uPA-PAI-1 .

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