Are the curli proteins CsgE and CsgF intrinsically disordered?

Curli are a type of proteinaceous cell surface filament produced by enteric bacteria such as and that facilitate cell adhesion and invasion, bio-film formation, and environmental persistence. Curli assembly involves 6 proteins encoded by the curli specific genes A, B, C, E, F, and G. Although CsgA is the major structural component of curli, CsgE, and CsgF, are thought to play important chaperone like functions in the assembly of CsgA into curli.

Membrane Curvature-sensing and Curvature-inducing Activity of Islet Amyloid Polypeptide and Its Implications for Membrane Disruption.

Islet amyloid polypeptide (IAPP) is a 37-amino acid amyloid protein intimately associated with pancreatic islet β-cell dysfunction and death in type II diabetes. In this study, we combine spectroscopic methods and microscopy to investigate α-helical IAPP-membrane interactions. Using light scattering and fluorescence microscopy, we observe that larger vesicles become smaller upon treatment with human or rat IAPP.

Beta-cell selective K(ATP)-channel activation protects beta-cells and human islets from human islet amyloid polypeptide induced toxicity.

Background And Aims: In type 2 diabetes mellitus (T2DM) chronic beta-cell stimulation and oligomers of aggregating human islet amyloid polypeptide (h-IAPP) cause beta-cell dysfunction and induce beta-cell apoptosis. Therefore we asked whether beta-cell rest prevents h-IAPP induced beta-cell apoptosis.

Materials And Methods: We induced beta-cell rest with a beta-cell selective K(ATP)-channel opener (K(ATP)CO) in RIN cells and human islets exposed to h-IAPP versus r-IAPP.

Annexin A5 directly interacts with amyloidogenic proteins and reduces their toxicity.

Protein misfolding is a central mechanism for the development of neurodegenerative diseases and type 2 diabetes mellitus. The accumulation of misfolded alpha-synuclein protein inclusions in the Lewy bodies of Parkinson's disease is thought to play a key role in pathogenesis and disease progression. Similarly, the misfolding of the beta-cell hormone human islet amyloid polypeptide (h-IAPP) into toxic oligomers plays a central role in the induction of beta-cell apoptosis in the context of type 2 diabetes.

MPEx: a tool for exploring membrane proteins.

Hydropathy plot methods form a cornerstone of membrane protein research, especially in the early stages of biochemical and structural characterization. Membrane Protein Explorer (MPEx), described in this article, is a refined and versatile hydropathy-plot software tool for analyzing membrane protein sequences. MPEx is highly interactive and facilitates the characterization and identification of favorable protein transmembrane regions using experiment-based physical and biological hydrophobicity scales.

Structure of alpha-helical membrane-bound human islet amyloid polypeptide and its implications for membrane-mediated misfolding.

Human islet amyloid polypeptide (hIAPP) misfolding is thought to play an important role in the pathogenesis of type II diabetes mellitus. It has recently been shown that membranes can catalyze the misfolding of hIAPP via an alpha-helical intermediate of unknown structure. To better understand the mechanism of membrane-mediated misfolding, we used site-directed spin labeling and EPR spectroscopy to generate a three-dimensional structural model of this membrane-bound form.

Folding amphipathic helices into membranes: amphiphilicity trumps hydrophobicity.

High amphiphilicity is a hallmark of interfacial helices in membrane proteins and membrane-active peptides, such as toxins and antimicrobial peptides. Although there is general agreement that amphiphilicity is important for membrane-interface binding, an unanswered question is its importance relative to simple hydrophobicity-driven partitioning. We have examined this fundamental question using measurements of the interfacial partitioning of a family of 17-residue amidated-acetylated peptides into both neutral and anionic lipid vesicles.

Membrane interaction of islet amyloid polypeptide.

Increasing evidence suggests that the misfolding and deposition of IAPP plays an important role in the pathogenesis of type II, or non-insulin-dependent diabetes mellitus (T2DM). Membranes have been implicated in IAPP-dependent toxicity in several ways: Lipid membranes have been shown to promote the misfolding and aggregation of IAPP. Thus, potentially toxic forms of IAPP can be generated when IAPP interacts with cellular membranes.

Inhibition of human IAPP fibril formation does not prevent beta-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP.

Type 2 diabetes mellitus (T2DM) is characterized by an approximately 60% deficit in beta-cell mass, increased beta-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). Human IAPP (hIAPP) forms oligomers, leading to either amyloid fibrils or toxic oligomers in an aqueous solution in vitro. Either application of hIAPP on or overexpression of hIAPP in cells induces apoptosis.

Lipid membranes modulate the structure of islet amyloid polypeptide.

The 37-residue islet amyloid polypeptide (IAPP) is thought to play an important role in the pathogenesis of type II diabetes. Despite a growing body of evidence implicating membrane interaction in IAPP toxicity, the membrane-bound form has not yet been well characterized. Here we used circular dichroism (CD) and fluorescence spectroscopy to investigate the molecular details of the interaction of IAPP with lipid membranes of varying composition.

Identifying structural features of fibrillar islet amyloid polypeptide using site-directed spin labeling.

Pancreatic amyloid deposits, composed primarily of the 37-residue islet amyloid polypeptide (IAPP), are a characteristic feature found in more than 90% of patients with type II diabetes. Although IAPP amyloid deposits are associated with areas of pancreatic islet beta-cell dysfunction and depletion and are thought to play a role in disease, their structure is unknown. We used electron paramagnetic resonance spectroscopy to analyze eight spin-labeled derivatives of IAPP in an effort to determine structural features of the peptide.

Global structural changes in annexin 12. The roles of phospholipid, Ca2+, and pH.

Ca2+-dependent membrane interaction has long been recognized as a general property of the annexin (ANX) family of proteins. More recently, it has become clear that ANXs can also undergo Ca2+-independent membrane interactions at mildly acidic pH. Here we use site-directed spin labeling in combination with circular dichroism and biochemical labeling methods to compare the structure and membrane topography of these two different membrane-bound forms of ANX12.