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An overview of the importance of conformational flexibility in gene regulation by the transcription factors.

Khan SH, Kumar R - J Biophys (2010)

Bottom Line: A number of proteins with intrinsically disordered (ID) regions/domains are reported to be found disproportionately higher in transcription factors.In the recent years there has been growing evidence suggesting that an induced fit-like process leads to imposition of folded functional structure in these ID domains on which large multiprotein complexes are built.These multiprotein complexes may eventually dictate the final outcome of the gene regulation by the transcription factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Sciences, The Commonwealth Medical College, Scranton, PA 18510, USA.

ABSTRACT
A number of proteins with intrinsically disordered (ID) regions/domains are reported to be found disproportionately higher in transcription factors. Available evidences suggest that presence of ID region/domain within a transcription factor plays an important role in its biological functions. These ID sequences provide large flexible surfaces that can allow them to make more efficient physical and functional interactions with their target partners. Since transcription factors regulate expression of target genes by interacting with specific coregulatory proteins, these ID regions/domains can be used as a platform for such large macromolecular interactions, and may represent a mechanism for regulation of cellular processes. The precise structural basis for the function of these ID regions/domains of the transcription factors remains to be determined. In the recent years there has been growing evidence suggesting that an induced fit-like process leads to imposition of folded functional structure in these ID domains on which large multiprotein complexes are built. These multiprotein complexes may eventually dictate the final outcome of the gene regulation by the transcription factors.

No MeSH data available.


A model showing possible events/factors that may alter conformation of an ID domain/region of transcription factors to fold into a functionally active form. (a) An ID domain/region without any defined structure ((a) blue) may adopt a set of partially folded conformation ((b) red) due to specific events/factors shown here. This conformation may suit well for specific interactions with binding partners (purple) and result in functionally active conformation ((c) green) under physiological conditions.
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fig1: A model showing possible events/factors that may alter conformation of an ID domain/region of transcription factors to fold into a functionally active form. (a) An ID domain/region without any defined structure ((a) blue) may adopt a set of partially folded conformation ((b) red) due to specific events/factors shown here. This conformation may suit well for specific interactions with binding partners (purple) and result in functionally active conformation ((c) green) under physiological conditions.

Mentions: It is a well established fact that there are a number of proteins often known as coregulatory proteins that make physical and functional interactions with DNA-bound transcription factors and participate in their transcriptional activation function [17]. These coregulators act as coactivators or corepressors depending upon the up- or down-regulation of the target gene by specific transcription factor [17]. Of course, addition of several additional cofactors cannot be ruled out that may be involved either directly or indirectly; some of them are ubiquitous, while others cell-specific [17]. In fact, for many transcription factors, it has been reported that their effects on transcriptional activity may be cell- and promoter-specific and potential explanation for these effects can be attributed to the formation of the assembly of transcription factor with other coregulatory proteins in a particular cellular setup [17]. Thus, specific combination of transcription factor and coactivators/corepressors results in the specific control of particular genes [17]. But the obvious questions then come to mind: how is the choice of coregulator interaction with specific transcription factor made? Some of the explanation for this can be provided from the fact that differing surfaces of the transcription factor are important for regulation of various genes [17]. There are several reports showing that protein:protein interactions may result in induced-fit alterations in the structure formation in ID region of the transcription factors [5]. In Figure 1, we have illustrated a model of binding/folding for ID domains/regions under physiological conditions.


An overview of the importance of conformational flexibility in gene regulation by the transcription factors.

Khan SH, Kumar R - J Biophys (2010)

A model showing possible events/factors that may alter conformation of an ID domain/region of transcription factors to fold into a functionally active form. (a) An ID domain/region without any defined structure ((a) blue) may adopt a set of partially folded conformation ((b) red) due to specific events/factors shown here. This conformation may suit well for specific interactions with binding partners (purple) and result in functionally active conformation ((c) green) under physiological conditions.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2821642&req=5

fig1: A model showing possible events/factors that may alter conformation of an ID domain/region of transcription factors to fold into a functionally active form. (a) An ID domain/region without any defined structure ((a) blue) may adopt a set of partially folded conformation ((b) red) due to specific events/factors shown here. This conformation may suit well for specific interactions with binding partners (purple) and result in functionally active conformation ((c) green) under physiological conditions.
Mentions: It is a well established fact that there are a number of proteins often known as coregulatory proteins that make physical and functional interactions with DNA-bound transcription factors and participate in their transcriptional activation function [17]. These coregulators act as coactivators or corepressors depending upon the up- or down-regulation of the target gene by specific transcription factor [17]. Of course, addition of several additional cofactors cannot be ruled out that may be involved either directly or indirectly; some of them are ubiquitous, while others cell-specific [17]. In fact, for many transcription factors, it has been reported that their effects on transcriptional activity may be cell- and promoter-specific and potential explanation for these effects can be attributed to the formation of the assembly of transcription factor with other coregulatory proteins in a particular cellular setup [17]. Thus, specific combination of transcription factor and coactivators/corepressors results in the specific control of particular genes [17]. But the obvious questions then come to mind: how is the choice of coregulator interaction with specific transcription factor made? Some of the explanation for this can be provided from the fact that differing surfaces of the transcription factor are important for regulation of various genes [17]. There are several reports showing that protein:protein interactions may result in induced-fit alterations in the structure formation in ID region of the transcription factors [5]. In Figure 1, we have illustrated a model of binding/folding for ID domains/regions under physiological conditions.

Bottom Line: A number of proteins with intrinsically disordered (ID) regions/domains are reported to be found disproportionately higher in transcription factors.In the recent years there has been growing evidence suggesting that an induced fit-like process leads to imposition of folded functional structure in these ID domains on which large multiprotein complexes are built.These multiprotein complexes may eventually dictate the final outcome of the gene regulation by the transcription factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Sciences, The Commonwealth Medical College, Scranton, PA 18510, USA.

ABSTRACT
A number of proteins with intrinsically disordered (ID) regions/domains are reported to be found disproportionately higher in transcription factors. Available evidences suggest that presence of ID region/domain within a transcription factor plays an important role in its biological functions. These ID sequences provide large flexible surfaces that can allow them to make more efficient physical and functional interactions with their target partners. Since transcription factors regulate expression of target genes by interacting with specific coregulatory proteins, these ID regions/domains can be used as a platform for such large macromolecular interactions, and may represent a mechanism for regulation of cellular processes. The precise structural basis for the function of these ID regions/domains of the transcription factors remains to be determined. In the recent years there has been growing evidence suggesting that an induced fit-like process leads to imposition of folded functional structure in these ID domains on which large multiprotein complexes are built. These multiprotein complexes may eventually dictate the final outcome of the gene regulation by the transcription factors.

No MeSH data available.