Structural Properties, Regulation and Posttranslational Modification of Signaling Proteins

Signal amplification converts a linear input to a steeply sigmoid output and is central to cellular functions. One canonical signal amplifying motif is zero-order ultrasensitivity through the posttranslational modification (PTM) cycle signaling proteins. The functionality of this signaling motif has been examined conventionally by supposing that the total amount of the protein substrates remains constant. However, covalent modification of signaling proteins often results in changes in their stability, which affects the abundance of the protein substrates. Here we use a mathematical model to explore the signal amplification properties in such scenarios. Our simulations indicate that PTM-induced protein stabilization brings the enzymes closer to saturation, and as a result, ultrasensitivity may emerge or is greatly enhanced, with a steeper sigmoidal response of higher magnitude and generally longer response time. In cases where PTM destabilizes the protein, ultrasensitivity can be regained through changes in the activities of the involved enzymes or from increased protein synthesis. Interestingly, ultrasensitivity is not limited to modified or unmodified protein substrates; the total protein substrate can also exhibit ultrasensitivity. It is conceivable that cells use inducible protein stabilization as a way to boost signal amplification while saving energy by keeping the protein substrate at low basal conditions.

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Neurofilaments and Paired Helical Filaments

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120357 ◽

1985 ◽

Vol 43 ◽

pp. 740-743

Author(s):

J. Metuzals

Keyword(s):

Animal Model ◽

Posttranslational Modifications ◽

Posttranslational Modification ◽

Giant Axon ◽

Paired Helical Filaments ◽

Squid Giant Axon ◽

In Vitro Experiments ◽

Thin Sections ◽

Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

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Geometric structural properties of bonded layers of chemically modified silicas

Journal of Chromatography A ◽

10.1016/s0021-9673(01)91460-8 ◽

1988 ◽

Vol 447 (3) ◽

pp. 103-116 ◽

Cited By ~ 2

Author(s):

A Fadeev

Keyword(s):

Structural Properties ◽

Chemically Modified ◽

Chemically Modified Silicas

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Electronic, vibrational and structural properties of alkali halide clusters

Physica B Condensed Matter ◽

10.1016/s0921-4526(84)92608-5 ◽

1984 ◽

Vol 127 (1-3) ◽

pp. 214-218 ◽

Cited By ~ 14

Author(s):

T MARTIN

Keyword(s):

Structural Properties ◽

Alkali Halide

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Newborn's Preference for Faces

European Psychologist ◽

10.1027/1016-9040.1.3.200 ◽

1996 ◽

Vol 1 (3) ◽

pp. 200-205 ◽

Cited By ~ 12

Author(s):

Carlo Umiltà ◽

Francesca Simion ◽

Eloisa Valenza

Keyword(s):

Visual System ◽

Structural Properties ◽

Sensory Properties ◽

Human Face ◽

System Experiment ◽

Face Experiment

Four experiments were aimed at elucidating some aspects of the preference for facelike patterns in newborns. Experiment 1 showed a preference for a stimulus whose components were located in the correct arrangement for a human face. Experiment 2 showed a preference for stimuli that had optimal sensory properties for the newborn visual system. Experiment 3 showed that babies directed their attention to a facelike pattern even when it was presented simultaneously with a non-facelike stimulus with optimal sensory properties. Experiment 4 showed the preference for facelike patterns in the temporal hemifield but not in the nasal hemifield. It was concluded that newborns' preference for facelike patterns reflects the activity of a subcortical system which is sensitive to the structural properties of the stimulus.

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