4TSH
A Novel Protein Fold Forms an Intramolecular Lock to Stabilize the Tertiary Structure of Streptococcus mutans Adhesin P1
Summary for 4TSH
| Entry DOI | 10.2210/pdb4tsh/pdb |
| Descriptor | Surface protein adhesin, CALCIUM ION, MAGNESIUM ION, ... (5 entities in total) |
| Functional Keywords | adhesin, streptococcus, intramolecular lock, complex, cell adhesion |
| Biological source | Streptococcus mutans More |
| Total number of polymer chains | 2 |
| Total formula weight | 69129.77 |
| Authors | Heim, K.P.,Kailasan, S.,McKenna, R.,Brady, L.J. (deposition date: 2014-06-18, release date: 2014-10-22, Last modification date: 2024-10-23) |
| Primary citation | Heim, K.P.,Crowley, P.J.,Long, J.R.,Kailasan, S.,McKenna, R.,Brady, L.J. An intramolecular lock facilitates folding and stabilizes the tertiary structure of Streptococcus mutans adhesin P1. Proc.Natl.Acad.Sci.USA, 111:15746-15751, 2014 Cited by 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. PubMed: 25331888DOI: 10.1073/pnas.1413018111 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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