title: Staphylococcus aureusSdrE captures complement factor H's C-terminus via a novel 'close, dock, lock and latch' mechanism for complement evasion.
abstract: Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. TheStaphylococcus aureussurface protein serine-aspartate repeat protein E (SdrE) was previously reported to bind human CFH as an immune-evasion tactic. However, the molecular mechanism underlying SdrE-CFH-mediated immune evasion remains unknown. In the present study, we identified a novel region at CFH's C-terminus (CFH1206-1226), which binds SdrE N2 and N3 domains (SdrEN2N3) with high affinity, and determined the crystal structures of apo-SdrEN2N3and the SdrEN2N3-CFH1206-1226complex. Comparison of the structure of the CFH-SdrE complex with other CFH structures reveals that CFH's C-terminal tail flips from the main body to insert into the ligand-binding groove of SdrE. In addition, SdrEN2N3adopts a 'close' state in the absence of CFH, which undergoes a large conformational change on CFH binding, suggesting a novel 'close, dock, lock and latch' (CDLL) mechanism for SdrE to recognize its ligand. Our findings imply that SdrE functions as a 'clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface ofS. aureusfor complement evasion.
authors.affiliation: School of Life Science, Anhui University, 111 Jiulong Road, Hefei 230601, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, CAS Center for Excellence in Biomacromolecules, Collaborative Innovation Center of Chemistry for Life Sciences, and School of Life Sciences, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China.|Key Laboratory of Structural Biology, Chinese Academy of Sciences, 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Minhao
authors.initials: M
authors.lastname: Wu
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, CAS Center for Excellence in Biomacromolecules, Collaborative Innovation Center of Chemistry for Life Sciences, and School of Life Sciences, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China.|Key Laboratory of Structural Biology, Chinese Academy of Sciences, 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Tianrong
authors.initials: T
authors.lastname: Hang
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, CAS Center for Excellence in Biomacromolecules, Collaborative Innovation Center of Chemistry for Life Sciences, and School of Life Sciences, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China.|Key Laboratory of Structural Biology, Chinese Academy of Sciences, 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Chengliang
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Life Science, Anhui University, 111 Jiulong Road, Hefei 230601, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Life Science, Anhui University, 111 Jiulong Road, Hefei 230601, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Pan
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, CAS Center for Excellence in Biomacromolecules, Collaborative Innovation Center of Chemistry for Life Sciences, and School of Life Sciences, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China.|Key Laboratory of Structural Biology, Chinese Academy of Sciences, 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Jianye
authors.initials: J
authors.lastname: Zang
authors.affiliation: School of Life Science, Anhui University, 111 Jiulong Road, Hefei 230601, China xuanzbin@ustc.edu.cn zhmin07@ustc.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, CAS Center for Excellence in Biomacromolecules, Collaborative Innovation Center of Chemistry for Life Sciences, and School of Life Sciences, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China xuanzbin@ustc.edu.cn zhmin07@ustc.edu.|Key Laboratory of Structural Biology, Chinese Academy of Sciences, 96 Jinzhai Road, Hefei, Anhui 230026, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D001059:Apoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D017242:Complement Factor H / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D057131:Immune Evasion; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D058767:Protein Unfolding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D001059:Apoproteins; D001426:Bacterial Proteins; C493495:CFH protein, human; D008024:Ligands; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C118507:SdrE protein, Staphylococcus aureus; D017242:Complement Factor H
keywords: Staphylococcus aureus SdrE; complement factor H; crystal structure; immune evasion mechanism; ligand recognition