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Structural mechanism for modulation of functional amyloid and biofilm formation by Staphylococcal Bap protein switch
- Source :
- EMBO J, Academica-e. Repositorio Institucional de la Universidad Pública de Navarra, instname
- Publication Year :
- 2021
- Publisher :
- EMBO Press, 2021.
-
Abstract
- The Staphylococcal Bap proteins sense environmental signals (such as pH, [Ca2+]) to build amyloid scaffold biofilm matrices via unknown mechanisms. We here report the crystal structure of the aggregation-prone region of Staphylococcus aureus Bap which adopts a dumbbell-shaped fold. The middle module (MM) connecting the N-terminal and C-terminal lobes consists of a tandem of novel double-Ca2+-binding motifs involved in cooperative interaction networks, which undergoes Ca2+-dependent order–disorder conformational switches. The N-terminal lobe is sufficient to mediate amyloid aggregation through liquid–liquid phase separation and maturation, and subsequent biofilm formation under acidic conditions. Such processes are promoted by disordered MM at low [Ca2+] but inhibited by ordered MM stabilized by Ca2+ binding, with inhibition efficiency depending on structural integrity of the interaction networks. These studies illustrate a novel protein switch in pathogenic bacteria and provide insights into the mechanistic understanding of Bap proteins in modulation of functional amyloid and biofilm formation, which could be implemented in the anti-biofilm drug design. This work was supported by grants from the National Natural Science Foundation of China (No. 31872712), the National Key Research and Development Project of China (2016YFA0500700), the Beijing Advanced Innovation Center for Structural Biology, the Tsinghua-Peking Joint Center for Life Sciences, to X.F.
- Subjects :
- Amyloid
Staphylococcus aureus
Biology
medicine.disease_cause
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Bacterial Proteins
Calcium-binding protein
Sense (molecular biology)
medicine
Molecular Biology
Cell Aggregation
030304 developmental biology
0303 health sciences
General Immunology and Microbiology
Novel protein
General Neuroscience
Biofilm
Biofilm associated protein
Structural integrity
Articles
Liquid-liquid phase separation
Biofilms
Amyloid aggregation
Functional amyloid
Biophysics
Order-disorder conformational switches
Calcium
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- EMBO J, Academica-e. Repositorio Institucional de la Universidad Pública de Navarra, instname
- Accession number :
- edsair.doi.dedup.....a628dfdc5c9d1d972e2e324dd2998fcc