Leucine-rich hydrophobic clusters promote folding of the N-terminus of the intrinsically disordered transactivation domain of p53

L. Michel Espinoza-Fonseca

doi:10.1016/j.febslet.2008.12.060

Leucine-rich hydrophobic clusters promote folding of the N-terminus of the intrinsically disordered transactivation domain of p53

L. Michel Espinoza-Fonseca

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

Molecular dynamics simulations have been performed on the intrinsically disordered 39-residue N-terminal transactivation domain of p53 (p53_1-39). Simulations not only revealed that p53_1-39 is natively compact, but also possesses a folded structure. Furthermore, leucine-rich hydrophobic clusters were found to play a crucial role in the formation and stabilization of the folded structure of p53_1-39. Collapsing in the sub-microsecond timescale might allow for rapid conformational turnovers of p53_1-39, necessary for its efficient transactivation activity and modulation. Fast collapsing might be the result of unique conformational landscapes, featuring several energy minima separated by small energy barriers. It is suggested that IDPs with highly specialized functions in the cell, such as transactivation, possibly display more ordered patterns than their less specialized counterparts.

Original language	English (US)
Pages (from-to)	556-560
Number of pages	5
Journal	FEBS Letters
Volume	583
Issue number	3
DOIs	https://doi.org/10.1016/j.febslet.2008.12.060
State	Published - Feb 4 2009
Externally published	Yes

Bibliographical note

Funding Information:
The author was supported in part by grants from Barcelona Supercomputing Center and CONACYT. The author acknowledges the computer resources, technical expertise and assistance provided by the Barcelona Supercomputing Center.

Keywords

Intrinsically disordered protein
Leucine-rich hydrophobic cluster
Molecular dynamics simulation
Protein folding
p53 transactivation domain

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10.1016/j.febslet.2008.12.060

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title = "Leucine-rich hydrophobic clusters promote folding of the N-terminus of the intrinsically disordered transactivation domain of p53",

abstract = "Molecular dynamics simulations have been performed on the intrinsically disordered 39-residue N-terminal transactivation domain of p53 (p531-39). Simulations not only revealed that p531-39 is natively compact, but also possesses a folded structure. Furthermore, leucine-rich hydrophobic clusters were found to play a crucial role in the formation and stabilization of the folded structure of p531-39. Collapsing in the sub-microsecond timescale might allow for rapid conformational turnovers of p531-39, necessary for its efficient transactivation activity and modulation. Fast collapsing might be the result of unique conformational landscapes, featuring several energy minima separated by small energy barriers. It is suggested that IDPs with highly specialized functions in the cell, such as transactivation, possibly display more ordered patterns than their less specialized counterparts.",

keywords = "Intrinsically disordered protein, Leucine-rich hydrophobic cluster, Molecular dynamics simulation, Protein folding, p53 transactivation domain",

author = "Espinoza-Fonseca, \{L. Michel\}",

note = "Funding Information: The author was supported in part by grants from Barcelona Supercomputing Center and CONACYT. The author acknowledges the computer resources, technical expertise and assistance provided by the Barcelona Supercomputing Center. ",

year = "2009",

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doi = "10.1016/j.febslet.2008.12.060",

language = "English (US)",

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T1 - Leucine-rich hydrophobic clusters promote folding of the N-terminus of the intrinsically disordered transactivation domain of p53

AU - Espinoza-Fonseca, L. Michel

N1 - Funding Information: The author was supported in part by grants from Barcelona Supercomputing Center and CONACYT. The author acknowledges the computer resources, technical expertise and assistance provided by the Barcelona Supercomputing Center.

PY - 2009/2/4

Y1 - 2009/2/4

N2 - Molecular dynamics simulations have been performed on the intrinsically disordered 39-residue N-terminal transactivation domain of p53 (p531-39). Simulations not only revealed that p531-39 is natively compact, but also possesses a folded structure. Furthermore, leucine-rich hydrophobic clusters were found to play a crucial role in the formation and stabilization of the folded structure of p531-39. Collapsing in the sub-microsecond timescale might allow for rapid conformational turnovers of p531-39, necessary for its efficient transactivation activity and modulation. Fast collapsing might be the result of unique conformational landscapes, featuring several energy minima separated by small energy barriers. It is suggested that IDPs with highly specialized functions in the cell, such as transactivation, possibly display more ordered patterns than their less specialized counterparts.

AB - Molecular dynamics simulations have been performed on the intrinsically disordered 39-residue N-terminal transactivation domain of p53 (p531-39). Simulations not only revealed that p531-39 is natively compact, but also possesses a folded structure. Furthermore, leucine-rich hydrophobic clusters were found to play a crucial role in the formation and stabilization of the folded structure of p531-39. Collapsing in the sub-microsecond timescale might allow for rapid conformational turnovers of p531-39, necessary for its efficient transactivation activity and modulation. Fast collapsing might be the result of unique conformational landscapes, featuring several energy minima separated by small energy barriers. It is suggested that IDPs with highly specialized functions in the cell, such as transactivation, possibly display more ordered patterns than their less specialized counterparts.

KW - Intrinsically disordered protein

KW - Leucine-rich hydrophobic cluster

KW - Molecular dynamics simulation

KW - Protein folding

KW - p53 transactivation domain

UR - https://www.scopus.com/pages/publications/58949101630

UR - https://www.scopus.com/pages/publications/58949101630#tab=citedBy

U2 - 10.1016/j.febslet.2008.12.060

DO - 10.1016/j.febslet.2008.12.060

M3 - Article

C2 - 19162020

AN - SCOPUS:58949101630

SN - 0014-5793

VL - 583

SP - 556

EP - 560

JO - FEBS Letters

JF - FEBS Letters

IS - 3

ER -

Leucine-rich hydrophobic clusters promote folding of the N-terminus of the intrinsically disordered transactivation domain of p53

Abstract

Bibliographical note

Keywords

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