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Structural mechanism for modulation of functional amyloid and biofilm formation by Staphylococcal Bap protein switch
Author(s) -
Ma Junfeng,
Cheng Xiang,
Xu Zhonghe,
Zhang Yikan,
Valle Jaione,
Fan Shilong,
Zuo Xiaobing,
Lasa Iñigo,
Fang Xianyang
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020107500
Subject(s) - biofilm , chemistry , biophysics , amyloid (mycology) , staphylococcus aureus , bacteria , microbiology and biotechnology , biochemistry , biology , inorganic chemistry , genetics
The Staphylococcal Bap proteins sense environmental signals (such as pH, [Ca 2+ ]) 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‐Ca 2+ ‐binding motifs involved in cooperative interaction networks, which undergoes Ca 2+ ‐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 [Ca 2+ ] but inhibited by ordered MM stabilized by Ca 2+ 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.