Can proteins be intrinsically disordered inside a membrane?

Kjærgaard, Magnus

doi:10.4161/21690707.2014.984570

Cited by 9 publications

(9 citation statements)

References 44 publications

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“…Thus, it is not surprising that in addition to their ordered domains, many enzymes, transport, and membrane proteins have numerous, and often long, functional IDPRs (94 -98). Furthermore, it has been recently hypothesized that even membrane-embedded domains of multipass transmembrane proteins could be disordered (40). In this model, disordered membrane proteins are suggested to have fully formed secondary structure, but little tertiary structure, and the sequence signature for disorder in membrane proteins is likely to be reversed, with disordered transmembrane proteins being more hydrophobic than their folded counterparts (40).…”

Section: Natural Abundance Of Idps: Where Do You Not Find Disorder?mentioning

confidence: 99%

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins

Uversky

2016

Journal of Biological Chemistry

190

182

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Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs.Brief Introduction: Why Those Proteins Are Clouds and Why Those Clouds Are Dancing "Dancing protein clouds" is a joke from a time when the newly born field of protein intrinsic disorder was trying to find an appropriate term to describe biologically active proteins without unique structures. The need for a specific term was determined by the clear recognition that those structureless functional proteins were fundamentally different from the "normal" globular proteins that used information encoded in their amino acid sequences to fold into specific, aperiodic crystal-like structures needed for specific biological functions. Fig. 1 reflects these attempts by representing different terms used in literature to describe such "strange" or "abnormal" proteins and shows that the "dancing protein clouds" expression is formed by superimposing "dancing proteins" and "protein clouds" descriptors. Although the phrase "dancing protein clouds" sounds like a parody, the term actually has deep meanings. The presence of a unique structure in a given protein means that when one would look at the sample containing this protein, s/he would find that all protein molecules are alike, that the structure of an individual molecule barely changes over time, and that the ensemble-averaged (or time-averaged) structure is identical, or at least very similar, to the structures of all individual protein molecules in that sample. In other words, if one would overlay all those individual structures, a crisp and clear image would be generated, similar to those found in the Protein Data Bank (PDB), and this ensemble-averaged structure would not change much over time. On the other hand, the lack of a unique structure in a given protein would create a highly dynamic ensemble, members of which would possess very different structures at any given moment, and the structure of any given molecule would change dramatically over time (therefore the "dancing protein" analogy). If one would try to overlay all those structures,...

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Section: Natural Abundance Of Idps: Where Do You Not Find Disorder?mentioning

confidence: 99%

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins

Uversky

2016

Journal of Biological Chemistry

190

182

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“… 25 Membrane-type 1 matrix metalloproteinase is one of the proteases that degrade extracellular matrix proteins, membrane proteins, and other proteins. 26 Interestingly, Kjaergaard et al 27 have reported on unstructured or disordered regions (DRs) in membrane proteins. These DRs are important for signal transduction and are extremely susceptible to proteolysis, thereby directly signaling for rapid degradation.…”

Section: Discussionmentioning

confidence: 99%

“…These DRs are important for signal transduction and are extremely susceptible to proteolysis, thereby directly signaling for rapid degradation. 27 , 28 From GlobPlot2.3 ( http://globplot.embl.de ), there are 4 DRs in the AQP3 protein: AA135-157, AA182-188, AA208-218, and AA269-276. 11 Membrane-type 1 matrix metalloproteinase and other proteases might bind these DRs of both mature (membranous) and nascent AQP3 proteins in dysplastic epithelial cells and tumor cells, resulting in degradation of the DRs and surrounding peptides.…”

Section: Discussionmentioning

confidence: 99%

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Assessing the Expression of Aquaporin 3 Antigen-Recognition Sites in Oral Squamous Cell Carcinoma

Udompatanakorn

Yada

Matsuo

2019

Applied Immunohistochemistry &Amp; Molecular Morphology

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Aquaporin 3 (AQP3) serves as a water and glycerol transporter facilitating epithelial cell hydration. Recently, the involvement of AQP3 in cancers has been reported. However, the immunohistochemical expression of AQP3 in carcinomas remains controversial. We hypothesized that differences in aquaporin 3 antigen recognition (AQP3 AR) may influence their expressions. Thus, our study aimed to assess the immunostaining patterns of 3 AQP3 AR sites in oral squamous cell carcinoma (OSCC) and to compare the adjacent areas of high-grade epithelial dysplasia (HG-ED) and normal oral mucosa (NOM). The study group included formalin-fixed OSCC samples (n=51) with adjacent regions of HG-ED (n=12) and NOM (n=51). The tissues were stained with anti-AQP3 antibodies (AR sites at amino acid (AA) 250-C terminus, AA180-228, and N terminus AA1-80) by immunohistochemistry. Our results showed that strong membranous immunostaining was observed for AQP3 AR sites at the AA250-C terminus and AA180-228 in all the samples for NOM and weak AQP3 immunostaining for both the AR sites in all the 12 samples for HG-ED. The invasive front of OSCC samples showed that AQP3 AR at the AA250-C terminus decreased in 42/51 samples (82.4%) and AA180-228 in 47/51 samples (92.2%). Conversely, in the AQP3 AR site at N terminus AA1-80, all samples of the NOM showed negative or slightly positive staining in the cytoplasm of the lower layers. AQP3 expression was increased in 12/12 cases (100%) and 46/51 cases (90.2%) in the HG-ED and invasive front of OSCC, respectively. AQP3 may be used as a biomarker for detecting malignant transformations. AQP3 AR site differences influence their immunohistochemical expression in OSCC.

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“…The membrane-embedded IDPs/IDPRs will have to be minimally organized into backbone hydrogen bonds internally, most likely in an -helical secondary structure. The helical structure in the bilayer region resembles soluble PMG or MG (Kjaergaard 2015 ).…”

Section: Idps/idprs-membrane Interactions: a Biophysical Studymentioning

confidence: 99%

Insights into Membrane Curvature Sensing and Membrane Remodeling by Intrinsically Disordered Proteins and Protein Regions

2022

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Cellular membranes are highly dynamic in shape. They can rapidly and precisely regulate their shape to perform various cellular functions. The protein’s ability to sense membrane curvature is essential in various biological events such as cell signaling and membrane trafficking. As they are bound, these curvature-sensing proteins may also change the local membrane shape by one or more curvature driving mechanisms. Established curvature-sensing/driving mechanisms rely on proteins with specific structural features such as amphipathic helices and intrinsically curved shapes. However, the recent discovery and characterization of many proteins have shattered the protein structure–function paradigm, believing that the protein functions require a unique structural feature. Typically, such structure-independent functions are carried either entirely by intrinsically disordered proteins or hybrid proteins containing disordered regions and structured domains. It is becoming more apparent that disordered proteins and regions can be potent sensors/inducers of membrane curvatures. In this article, we outline the basic features of disordered proteins and regions, the motifs in such proteins that encode the function, membrane remodeling by disordered proteins and regions, and assays that may be employed to investigate curvature sensing and generation by ordered/disordered proteins. Graphical Abstract

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Can proteins be intrinsically disordered inside a membrane?

Cited by 9 publications

References 44 publications

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins

Assessing the Expression of Aquaporin 3 Antigen-Recognition Sites in Oral Squamous Cell Carcinoma

Insights into Membrane Curvature Sensing and Membrane Remodeling by Intrinsically Disordered Proteins and Protein Regions

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