4NSM

crystal structure of the streptococcal collagen-like protein 2 globular domain from invasive M3-type group A Streptococcus

Summary for 4NSM

• Entry DOI: 10.2210/pdb4nsm/pdb
• Descriptor: Collagen-like protein SclB, SULFATE ION, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: six-helix bundle, structural protein
• Biological source: Streptococcus pyogenes
• Total number of polymer chains: 1
• Total formula weight: 10433.50

Authors

Berisio, R.,Squeglia, F.,Lukomski, S.,Bachert, B. (deposition date: 2013-11-28, release date: 2013-12-25, Last modification date: 2024-02-28)

Primary citation

Squeglia, F.,Bachert, B.,De Simone, A.,Lukomski, S.,Berisio, R.
The Crystal Structure of the Streptococcal Collagen-like Protein 2 Globular Domain from Invasive M3-type Group A Streptococcus Shows Significant Similarity to Immunomodulatory HIV Protein gp41.
J.Biol.Chem., 289:5122-5133, 2014

PubMed Abstract: The arsenal of virulence factors deployed by streptococci includes streptococcal collagen-like (Scl) proteins. These proteins, which are characterized by a globular domain and a collagen-like domain, play key roles in host adhesion, host immune defense evasion, and biofilm formation. In this work, we demonstrate that the Scl2.3 protein is expressed on the surface of invasive M3-type strain MGAS315 of Streptococcus pyogenes. We report the crystal structure of Scl2.3 globular domain, the first of any Scl. This structure shows a novel fold among collagen trimerization domains of either bacterial or human origin. Despite there being low sequence identity, we observed that Scl2.3 globular domain structurally resembles the gp41 subunit of the envelope glycoprotein from human immunodeficiency virus type 1, an essential subunit for viral fusion to human T cells. We combined crystallographic data with modeling and molecular dynamics techniques to gather information on the entire lollipop-like Scl2.3 structure. Molecular dynamics data evidence a high flexibility of Scl2.3 with remarkable interdomain motions that are likely instrumental to the protein biological function in mediating adhesive or immune-modulatory functions in host-pathogen interactions. Altogether, our results provide molecular tools for the understanding of Scl-mediated streptococcal pathogenesis and important structural insights for the future design of small molecular inhibitors of streptococcal invasion.

PubMed: 24356966
DOI: 10.1074/jbc.M113.523597

Experimental method

X-RAY DIFFRACTION (1.6 Å)