5WTB

Complex Structure of Staphylococcus aureus SdrE with human complement factor H

Summary for 5WTB

• Entry DOI: 10.2210/pdb5wtb/pdb
• Related: 5WTA
• Descriptor: Serine-aspartate repeat-containing protein E, Peptide from Complement factor H (2 entities in total)
• Functional Keywords: staphylococcus aureus, sdr family, complement factor h, complement evasion, cell adhesion
• Biological source: Staphylococcus aureus (strain Mu50 / ATCC 700699); More
• Cellular location: Secreted, cell wall ; Peptidoglycan-anchor : Q932F7; Secreted: P08603
• Total number of polymer chains: 8
• Total formula weight: 160823.95

Authors

Wu, M.,Zhang, Y.,Hang, T.,Wang, C.,Yang, Y.,Zang, J.,Zhang, M.,Zhang, X. (deposition date: 2016-12-10, release date: 2017-07-19, Last modification date: 2023-11-08)

Primary citation

Zhang, Y.,Wu, M.,Hang, T.,Wang, C.,Yang, Y.,Pan, W.,Zang, J.,Zhang, M.,Zhang, X.
Staphylococcus aureus SdrE captures complement factor H's C-terminus via a novel 'close, dock, lock and latch' mechanism for complement evasion
Biochem. J., 474:1619-1631, 2017

PubMed 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. The surface 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 (CFH), which binds SdrE N2 and N3 domains (SdrE) with high affinity, and determined the crystal structures of apo-SdrE and the SdrE-CFH complex. 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, SdrE adopts 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 of for complement evasion.

PubMed: 28258151
DOI: 10.1042/BCJ20170085

Experimental method

X-RAY DIFFRACTION (3.3 Å)