Crystal structure of the mucin-binding domain of Spr1345 from Streptococcus pneumoniae.
The surface protein Spr1345 from Streptococcus pneumoniae R6 is a 22-kDa mucin-binding protein (MucBP) involved in adherence and colonization of the human lung and respiratory tract. It is composed of a mucin-binding domain (MucBD) and a proline-rich domain (PRD) followed by an LPxTG motif, which is recognized and cleaved by sortase, resulting in a mature form of 171 residues (MF171) that is anchored to the cell wall. We found that the MucBD alone possesses comparable in vitro mucin-binding affinity to the mature form, and can be specifically enriched at the surface of human lung carcinoma A549 cells. Using single-wavelength anomalous dispersion (SAD) phasing method with the iodine signals, we solved the crystal structure of the MucBD at 2.0Å resolution, the first structure of MucBDs from pathogenic bacteria. The overall structure adopts an immunoglobulin-like fold with an elongated rod-like shape, composed of six anti-parallel β-strands and a long loop. Structural comparison suggested that the conserved C-terminal moiety may participate in the recognition of mucins. These findings provided structural insights into host-pathogen interaction mediated by mucins, which might be useful for designing novel vaccines and antibiotic drugs against human diseases caused by pneumococci.
School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China.
Yang
Y
Du
Yong-Xing
YX
He
Zhen-Yi
ZY
Zhang
Yi-Hu
YH
Yang
Wei-Wei
WW
Shi
Cécile
C
Frolet
Anne-Marie
AM
Di Guilmi
Thierry
T
Vernet
Cong-Zhao
CZ
Zhou
Yuxing
Y
Chen
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009077:Mucins / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013296:Streptococcus pneumoniae / Q000378:metabolism*
D001426:Bacterial Proteins; D009077:Mucins