Functional amyloids from bacterial biofilms – structural properties and interaction partners

Akbey, Ümit; Andreasen, Maria

doi:10.1039/d2sc00645f

Cited by 31 publications

(42 citation statements)

References 209 publications

(363 reference statements)

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“…FapC and CsgA are unfolded intrinsically disordered proteins (IDP). 5 TasA, however, has a globular folded protein fold. 5, 9 FapC has been predominantly characterized by biophysical techniques and low-resolution methods as a pure protein or with its interaction partners.…”

Section: Biological Contextmentioning

confidence: 99%

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Solution-state NMR Assignment and Secondary Structural Propensities of the Full-Length and Minimalistic-Truncated Prefibrillar Monomeric Form of Biofilm-Forming Functional-Amyloid FapC fromPseudomonas aeruginosa

Akbey

Byeon

et al. 2023

Preprint

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Functional bacterial amyloids provide structural scaffolding to bacterial biofilms. In contrast to the pathological amyloids, they have a role in vivo and are tightly regulated. Their presence is essential to the integrity of the bacterial communities surviving in biofilms and may cause serious health complications. Targeting amyloids in biofilms could be a novel approach to prevent chronic infections. However, structural information is very scarce on them in both soluble monomeric and insoluble fibrillar forms, hindering our molecular understanding and strategies to fight biofilm related diseases. Here, we present solution-state NMR assignment of 250 amino acid long biofilm-forming functional-amyloid FapC from Pseudomonas aeruginosa. We studied the full-length and shorter minimalistic-truncated FapC constructs without signal-sequence that is required for secretion. 91% and 100% backbone NH resonance assignment for FL and short constructs, respectively, indicates that soluble monomeric FapC is predominantly disordered, with sizeable secondary structural propensities mostly as PP2 helices, but also as alpha-helices and beta-sheets highlighting hotspots for fibrillation initiation interface. Shorter construct showing almost identical NMR chemical shifts highlights the promise of utilizing it for more demanding solid-state NMR studies that requires methods to alleviate signal redundancy due to almost identical repeat units. This study provides key NMR resonance assignment for future structural studies of soluble, pre-fibrillar and fibrillar forms of FapC.

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Section: Biological Contextmentioning

confidence: 99%

“…5 TasA, however, has a globular folded protein fold. 5, 9 FapC has been predominantly characterized by biophysical techniques and low-resolution methods as a pure protein or with its interaction partners. A high-resolution NMR based study with sequential signal assignments was missing.…”

Section: Biological Contextmentioning

confidence: 99%

Solution-state NMR Assignment and Secondary Structural Propensities of the Full-Length and Minimalistic-Truncated Prefibrillar Monomeric Form of Biofilm-Forming Functional-Amyloid FapC fromPseudomonas aeruginosa

Akbey

Byeon

et al. 2023

Preprint

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“…The resulting fibrils can in some cases lead to a novel pathological condition [ 13 ]. However, at the same time, the list of proteins and peptides that are naturally found in the amyloid state fulfilling a specific physiological role has exponentially increased in recent years [ 8 , 14 , 15 , 16 ]. These functional amyloids possess unique features that have been exploited by nature to provide a wide variety of physiological adaptations, such as mechanical support in bacterial biofilms, information exchange through the bacterial pili, and hydrophobic coating, among many others.…”

Section: The Amyloid Statementioning

confidence: 99%

Catalytically Active Amyloids as Future Bionanomaterials

Díaz-Espinoza

2022

Nanomaterials

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Peptides and proteins can aggregate into highly ordered and structured conformations called amyloids. These supramolecular structures generally have convergent features, such as the formation of intermolecular beta sheets, that lead to fibrillary architectures. The resulting fibrils have unique mechanical properties that can be exploited to develop novel nanomaterials. In recent years, sequences of small peptides have been rationally designed to self-assemble into amyloids that catalyze several chemical reactions. These amyloids exhibit reactive surfaces that can mimic the active sites of enzymes. In this review, I provide a state-of-the-art summary of the development of catalytically active amyloids. I will focus especially on catalytic activities mediated by hydrolysis, which are the most studied examples to date, as well as novel types of recently reported activities that promise to expand the possible repertoires. The combination of mechanical properties with catalytic activity in an amyloid scaffold has great potential for the development of future bionanomaterials aimed at specific applications.

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“…Functional bacterial amyloids (FuBA) are unique class of amyloid fibrils that have function in living organisms, and do not directly cause diseases as their pathologic relatives. [1][2][3][4][5][6] They are involved in many biological processes such as biofilm formation as a survival mechanism of bacteria to protect themselves under stress inducing hostile conditions. Although biofilm forming FuBAs do not directly cause diseases, they are indirectly mediating pathology through chronic bacterial infections, and leading to increased antimicrobial resistance.…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10][11] For a detailed review on this topic, we refer the reader to recent reviews. 6,12 In recent years, there has been large interest in the functional amyloids, their biological roles and biophysical characterization. Despite abundant biophysical information available on functional amyloids, structural insights have been elusive due to the difficulties in studying either monomeric intrinsically disordered protein (IDP) forms or amyloids fibril forming macroscopic filaments.…”

Section: Introductionmentioning

confidence: 99%

Identifying interaction interface betweenPseudomonasmajor biofilm forming functional amyloid FapC and disordered chaperone FapA during fibrillation deceleration

Byeon

Hansen

Jeffrey

et al. 2023

Preprint

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Functional bacterial amyloids (FuBA) are involved in biofilm formation in Pseudomonas aeruginosa. Biofilm forming bacterial colonies are difficult to treat, cause most of the chronic bacterial infections and are relevant in the context of antimicrobial resistance. Here in this work by focusing on the major biofilm forming FapC protein we demonstrate the initial steps of the chaperone aided amyloid formation. Solution NMR spectroscopy gave atomic resolution information on the prefibrillar soluble monomeric FapC that is an intrinsically disordered protein (IPD). Moreover, we show that the chaperone FapA within the same biofilm forming protein operon interacts with FapC. FapA is itself an IDP and remarkably slows down the FapC fibril formation without modifying the final fibril morphology. Monitoring of the small but significant chemical shift perturbations allowed the determination of the interaction interface which was not observed previously. To the best of our knowledge, our work provides the first atomic-level identification of a rather specific interaction of an IDP chaperone, FapA, to modulate and slow-down the functional amyloid protein FapC towards its path to mature fibril formation. Our results establish a better understanding of the functional amyloid formation in bacterial biofilms and its molecular level tuning or prevention by chaperones. We foresee that future therapeutic treatments of biofilms and relevant infections could emerged from these structural and mechanistic insights.

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Functional amyloids from bacterial biofilms – structural properties and interaction partners

Abstract: aggregation and amyloid formation have historically been linked with various diseases such as Alzheimer’s and Parkinson’s disease but recently functional amyloids have gained a great deal of interest in not...

Cited by 31 publications

References 209 publications

Solution-state NMR Assignment and Secondary Structural Propensities of the Full-Length and Minimalistic-Truncated Prefibrillar Monomeric Form of Biofilm-Forming Functional-Amyloid FapC fromPseudomonas aeruginosa

Solution-state NMR Assignment and Secondary Structural Propensities of the Full-Length and Minimalistic-Truncated Prefibrillar Monomeric Form of Biofilm-Forming Functional-Amyloid FapC fromPseudomonas aeruginosa

Catalytically Active Amyloids as Future Bionanomaterials

Identifying interaction interface betweenPseudomonasmajor biofilm forming functional amyloid FapC and disordered chaperone FapA during fibrillation deceleration

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