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A monomer-trimer model supports intermittent glucagon fibril growth.

Košmrlj A, Cordsen P, Kyrsting A, Otzen DE, Oddershede LB, Jensen MH - Sci Rep (2015)

Bottom Line: The growth probability is large at high and low concentrations and is reduced for intermediate glucagon concentrations.To explain this behavior we propose a simple model, where fibrils come in two forms, one built entirely from glucagon monomers and one entirely from glucagon trimers.The opposite building blocks act as fibril growth blockers, and this generic model reproduces experimental behavior well.

View Article: PubMed Central - PubMed

Affiliation: Harvard University, Department of Physics, 17 Oxford Street, Cambridge, MA 02138, USA.

ABSTRACT
We investigate in vitro fibrillation kinetics of the hormone peptide glucagon at various concentrations using confocal microscopy and determine the glucagon fibril persistence length 60μm. At all concentrations we observe that periods of individual fibril growth are interrupted by periods of stasis. The growth probability is large at high and low concentrations and is reduced for intermediate glucagon concentrations. To explain this behavior we propose a simple model, where fibrils come in two forms, one built entirely from glucagon monomers and one entirely from glucagon trimers. The opposite building blocks act as fibril growth blockers, and this generic model reproduces experimental behavior well.

No MeSH data available.


Related in: MedlinePlus

Schematic overview of the glucagon growth model showing (upper part) monomer-trimer equilibrium and (lower part) fibrillation process.Glucagon monomers are in equilibrium with glucagon trimers. Elongation of a fibril is a two-step process, which can be interrupted by binding of the other oligomer. Fibrils consist of either monomers or trimers but never a combination of the two. A glucagon trimer (monomer) can bind to a growing fibril end and then dissociate or elongate the fibril after conformational rearrangement. Filled triangles (circles) symbolize trimers (monomers) bound irreversibly to a fibril, while hollow triangles (circles) mean unbound trimers (monomers). A glucagon monomer (trimer) can also bind to a growing fibril end, but in this arrested state it prevents further attachment of glucagon trimers (monomers).
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f3: Schematic overview of the glucagon growth model showing (upper part) monomer-trimer equilibrium and (lower part) fibrillation process.Glucagon monomers are in equilibrium with glucagon trimers. Elongation of a fibril is a two-step process, which can be interrupted by binding of the other oligomer. Fibrils consist of either monomers or trimers but never a combination of the two. A glucagon trimer (monomer) can bind to a growing fibril end and then dissociate or elongate the fibril after conformational rearrangement. Filled triangles (circles) symbolize trimers (monomers) bound irreversibly to a fibril, while hollow triangles (circles) mean unbound trimers (monomers). A glucagon monomer (trimer) can also bind to a growing fibril end, but in this arrested state it prevents further attachment of glucagon trimers (monomers).

Mentions: To explain the intermittent fibril growth behavior we propose a model sketched in Fig. 3. In the bulk solution glucagon monomers are in equilibrium with glucagon trimers and these two components give rise to twisted and non-twisted fibrils, respectively. Successive binding of glucagon monomers to the twisted fibril end corresponds to the growing state, while binding of trimers to the twisted fibril end prevents further growth until the trimer is detached. During this time the twisted fibril appears to be in the arrested state. The opposite is true for non-twisted fibrils, which are formed from glucagon trimers, while glucagon monomers inhibit their growth.


A monomer-trimer model supports intermittent glucagon fibril growth.

Košmrlj A, Cordsen P, Kyrsting A, Otzen DE, Oddershede LB, Jensen MH - Sci Rep (2015)

Schematic overview of the glucagon growth model showing (upper part) monomer-trimer equilibrium and (lower part) fibrillation process.Glucagon monomers are in equilibrium with glucagon trimers. Elongation of a fibril is a two-step process, which can be interrupted by binding of the other oligomer. Fibrils consist of either monomers or trimers but never a combination of the two. A glucagon trimer (monomer) can bind to a growing fibril end and then dissociate or elongate the fibril after conformational rearrangement. Filled triangles (circles) symbolize trimers (monomers) bound irreversibly to a fibril, while hollow triangles (circles) mean unbound trimers (monomers). A glucagon monomer (trimer) can also bind to a growing fibril end, but in this arrested state it prevents further attachment of glucagon trimers (monomers).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355668&req=5

f3: Schematic overview of the glucagon growth model showing (upper part) monomer-trimer equilibrium and (lower part) fibrillation process.Glucagon monomers are in equilibrium with glucagon trimers. Elongation of a fibril is a two-step process, which can be interrupted by binding of the other oligomer. Fibrils consist of either monomers or trimers but never a combination of the two. A glucagon trimer (monomer) can bind to a growing fibril end and then dissociate or elongate the fibril after conformational rearrangement. Filled triangles (circles) symbolize trimers (monomers) bound irreversibly to a fibril, while hollow triangles (circles) mean unbound trimers (monomers). A glucagon monomer (trimer) can also bind to a growing fibril end, but in this arrested state it prevents further attachment of glucagon trimers (monomers).
Mentions: To explain the intermittent fibril growth behavior we propose a model sketched in Fig. 3. In the bulk solution glucagon monomers are in equilibrium with glucagon trimers and these two components give rise to twisted and non-twisted fibrils, respectively. Successive binding of glucagon monomers to the twisted fibril end corresponds to the growing state, while binding of trimers to the twisted fibril end prevents further growth until the trimer is detached. During this time the twisted fibril appears to be in the arrested state. The opposite is true for non-twisted fibrils, which are formed from glucagon trimers, while glucagon monomers inhibit their growth.

Bottom Line: The growth probability is large at high and low concentrations and is reduced for intermediate glucagon concentrations.To explain this behavior we propose a simple model, where fibrils come in two forms, one built entirely from glucagon monomers and one entirely from glucagon trimers.The opposite building blocks act as fibril growth blockers, and this generic model reproduces experimental behavior well.

View Article: PubMed Central - PubMed

Affiliation: Harvard University, Department of Physics, 17 Oxford Street, Cambridge, MA 02138, USA.

ABSTRACT
We investigate in vitro fibrillation kinetics of the hormone peptide glucagon at various concentrations using confocal microscopy and determine the glucagon fibril persistence length 60μm. At all concentrations we observe that periods of individual fibril growth are interrupted by periods of stasis. The growth probability is large at high and low concentrations and is reduced for intermediate glucagon concentrations. To explain this behavior we propose a simple model, where fibrils come in two forms, one built entirely from glucagon monomers and one entirely from glucagon trimers. The opposite building blocks act as fibril growth blockers, and this generic model reproduces experimental behavior well.

No MeSH data available.


Related in: MedlinePlus