A 'Collagen Hug' model for Staphylococcus aureus CNA binding to collagen.
The structural basis for the association of eukaryotic and prokaryotic protein receptors and their triple-helical collagen ligand remains poorly understood. Here, we present the crystal structures of a high affinity subsegment of the Staphylococcus aureus collagen-binding CNA as an apo-protein and in complex with a synthetic collagen-like triple helical peptide. The apo-protein structure is composed of two subdomains (N1 and N2), each adopting a variant IgG-fold, and a long linker that connects N1 and N2. The structure is stabilized by hydrophobic inter-domain interactions and by the N2 C-terminal extension that complements a beta-sheet on N1. In the ligand complex, the collagen-like peptide penetrates through a spherical hole formed by the two subdomains and the N1-N2 linker. Based on these two structures we propose a dynamic, multistep binding model, called the 'Collagen Hug' that is uniquely designed to allow multidomain collagen binding proteins to bind their extended rope-like ligand.
Zong
Yinong
Y
School of Optometry and Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Xu
Yi
Y
Liang
Xiaowen
X
Keene
Douglas R
DR
Höök
Agneta
A
Gurusiddappa
Shivasankarappa
S
Höök
Magnus
M
Narayana
Sthanam V L
SV
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D003094:Collagen / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013211:Staphylococcus aureus / Q000378:metabolism*; D020349:Surface Plasmon Resonance
D018829:Adhesins, Bacterial; D007074:Immunoglobulin G; D008024:Ligands; D010455:Peptides; C048165:adhesin, Staphylococcus aureus; D003094:Collagen; D004247:DNA