PDBsum entry 4m01

Cell adhesion

PDB id: 4m01

Contents

Protein chains

321 a.a.

Ligands

GOL ×6

Metals

_CA ×4

Waters ×1428

PDB id:

4m01

Name:

Cell adhesion

Title:

N terminal fragment(residues 245-575) of binding region of srap

Structure:

Serine-rich adhesin for platelets. Chain: a, b, c, d. Fragment: n-terminal fragment of binding region, unp residues 245- 575. Synonym: staphylococcus aureus surface protein a. Engineered: yes

Source:

Staphylococcus aureus. Organism_taxid: 93061. Strain: nctc 8325. Gene: srap. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.10Å R-factor: 0.160 R-free: 0.195

Authors:

Y.H.Yang,Y.L.Jiang,J.Zhang,L.Wang,Y.Chen,C.Z.Zhou

Key ref:

Y.H.Yang et al. (2014). Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells. Plos Pathog, 10, e1004169. PubMed id: 24901708 DOI: 10.1371/journal.ppat.1004169

Date:

01-Aug-13 Release date: 18-Jun-14

Protein chains

Q2FUW1  (SRAP_STAA8) -  Serine-rich adhesin for platelets from Staphylococcus aureus (strain NCTC 8325 / PS 47)

Seq: 2271 a.a.

Struc: 321 a.a.

DOI no: 10.1371/journal.ppat.1004169

Plos Pathog 10:e1004169 (2014)

PubMed id: 24901708

Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells.

Y.H.Yang, Y.L.Jiang, J.Zhang, L.Wang, X.H.Bai, S.J.Zhang, Y.M.Ren, N.Li, Y.H.Zhang, Z.Zhang, Q.Gong, Y.Mei, T.Xue, J.R.Zhang, Y.Chen, C.Z.Zhou.

ABSTRACT

Staphylococcus aureus, a Gram-positive bacterium causes a number of devastating human diseases, such as infective endocarditis, osteomyelitis, septic arthritis and sepsis. S. aureus SraP, a surface-exposed serine-rich repeat glycoprotein (SRRP), is required for the pathogenesis of human infective endocarditis via its ligand-binding region (BR) adhering to human platelets. It remains unclear how SraP interacts with human host. Here we report the 2.05 Å crystal structure of the BR of SraP, revealing an extended rod-like architecture of four discrete modules. The N-terminal legume lectin-like module specifically binds to N-acetylneuraminic acid. The second module adopts a β-grasp fold similar to Ig-binding proteins, whereas the last two tandem repetitive modules resemble eukaryotic cadherins but differ in calcium coordination pattern. Under the conditions tested, small-angle X-ray scattering and molecular dynamic simulation indicated that the three C-terminal modules function as a relatively rigid stem to extend the N-terminal lectin module outwards. Structure-guided mutagenesis analyses, in addition to a recently identified trisaccharide ligand of SraP, enabled us to elucidate that SraP binding to sialylated receptors promotes S. aureus adhesion to and invasion into host epithelial cells. Our findings have thus provided novel structural and functional insights into the SraP-mediated host-pathogen interaction of S. aureus.