4TSH

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

4TSH の概要

• エントリーDOI: 10.2210/pdb4tsh/pdb
• 分子名称: Surface protein adhesin, CALCIUM ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: adhesin, streptococcus, intramolecular lock, complex, cell adhesion
• 由来する生物種: Streptococcus mutans; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69129.77

構造登録者

Heim, K.P.,Kailasan, S.,McKenna, R.,Brady, L.J. (登録日: 2014-06-18, 公開日: 2014-10-22, 最終更新日: 2024-10-23)

主引用文献

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

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: 25331888
DOI: 10.1073/pnas.1413018111

実験手法

X-RAY DIFFRACTION (2 Å)