title: A clamp-like orientation of basic residues set in a parallelogram is essential for heparin binding.
abstract: While the majority of studies have focused on the biological roles of heparin-binding proteins, relatively little is known about their key residues and structural elements responsible for heparin interaction. In this study, we employed the IgG-binding domain B1 of Streptococcal protein G as a miniature scaffold to investigate how certain positively charged residues within the β-sheet conformation become favorable for heparin binding. By performing a series of arginine substitution mutations followed by gain-of-heparin-binding analysis, we deduced that a clamp-like orientation with discontinuous basic residues separated by ~ 5 Å with ~ 100° interior angle is advantageous for high heparin affinity.
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.|National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yi-Yun
authors.initials: YY
authors.lastname: Cheng
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chao-Sheng
authors.initials: CS
authors.lastname: Cheng
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.|Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Tian-Ren
authors.initials: TR
authors.lastname: Lee
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan. wayne@nhri.org.tw.
authors.forename: Wun-Shaing Wayne
authors.initials: WS
authors.lastname: Chang
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan. lslpc@life.nthu.edu.tw.|Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan. lslpc@life.nthu.edu.tw.
authors.forename: Ping-Chiang
authors.initials: PC
authors.lastname: Lyu
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D006493:Heparin / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding
chemical_list: D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D006493:Heparin
keywords: GB1; heparin binding; protein modeling