4TSH

A Novel Protein Fold Forms an Intramolecular Lock to Stabilize the Tertiary Structure of Streptococcus mutans Adhesin P1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.171 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

An intramolecular lock facilitates folding and stabilizes the tertiary structure of Streptococcus mutans adhesin P1.

Heim, K.P.Crowley, P.J.Long, J.R.Kailasan, S.McKenna, R.Brady, L.J.

(2014) Proc Natl Acad Sci U S A 111: 15746-15751

  • DOI: https://doi.org/10.1073/pnas.1413018111
  • Primary Citation of Related Structures:  
    4TSH

  • PubMed Abstract: 

    The cariogenic bacterium Streptococcus mutans uses adhesin P1 to adhere to tooth surfaces, extracellular matrix components, and other bacteria. A composite model of P1 based on partial crystal structures revealed an unusual complex architecture in which the protein forms an elongated hybrid alpha/polyproline type II helical stalk by folding back on itself to display a globular head at the apex and a globular C-terminal region at the base. The structure of P1's N terminus and the nature of its critical interaction with the C-terminal region remained unknown, however. We have cocrystallized a stable complex of recombinant N- and C-terminal fragments and here describe a previously unidentified topological fold in which these widely discontinuous domains are intimately associated. The structure reveals that the N terminus forms a stabilizing scaffold by wrapping behind the base of P1's elongated stalk and physically "locking" it into place. The structure is stabilized through a highly favorable ΔG(solvation) on complex formation, along with extensive hydrogen bonding. We confirm the functional relevance of this intramolecular interaction using differential scanning calorimetry and circular dichroism to show that disruption of the proper spacing of residues 989-1001 impedes folding and diminishes stability of the full-length molecule, including the stalk. Our findings clarify previously unexplained functional and antigenic properties of P1.


  • Organizational Affiliation

    Departments of Oral Biology and Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Surface protein adhesin121Streptococcus mutansMutation(s): 0 
Gene Names: spaP
UniProt
Find proteins for C9E3B4 (Streptococcus mutans)
Explore C9E3B4 
Go to UniProtKB:  C9E3B4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupC9E3B4
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Surface protein adhesin507Streptococcus mutansMutation(s): 0 
Gene Names: spaP
UniProt
Find proteins for C9E3B4 (Streptococcus mutans)
Explore C9E3B4 
Go to UniProtKB:  C9E3B4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupC9E3B4
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.171 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 197.521α = 90
b = 68.887β = 96.82
c = 81.278γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR)United StatesR01DE21789
National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR)United StatesR01DE08007
National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR)United StatesT90 DE021990-03

Revision History  (Full details and data files)

  • Version 1.0: 2014-10-22
    Type: Initial release
  • Version 1.1: 2014-11-05
    Changes: Database references
  • Version 1.2: 2014-11-19
    Changes: Database references
  • Version 1.3: 2017-09-27
    Changes: Advisory, Author supporting evidence, Database references, Derived calculations, Other, Source and taxonomy
  • Version 1.4: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.5: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description