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Proline and water stabilization of a universal two-step folding mechanism for β-turn formation in solution

Proline and water stabilization of a universal two-step folding mechanism for β-turn formation in solution
Proline and water stabilization of a universal two-step folding mechanism for β-turn formation in solution

The atomic scale process by which proteins fold into their functional forms in aqueous solutions is still not well understood. While there is clearly an interplay between the sequence of the protein and the surrounding water solvent that leads to highly specific and reproducible folding in nature, there is still an ongoing debate concerning how water molecules aid in driving the folding process. By using a combination of techniques that provide information at the atomic level - neutron and X-ray diffraction and computer simulations - the mechanism of folding in a series of peptides that only vary with respect to the central side-chain residue has been determined. Specifically, β-turn formation for the KGXGK peptide (where X = P, G, S or L) occurs via a two-step water-driven attraction between specific sites on the peptide backbone. This proposed mechanism suggests that the site-specific hydration of the backbone facilitates the initial stages of protein folding and that this hydration interaction in combination with the presence of proline in the i + 1 position helps to stabilize the folded and intermediate folding state of the peptide in solution, leading to a greater propensity for PG containing sequences to occur in β-turns in proteins.

0002-7863
7301-7312
Steinke, Nicola
c5b12ef5-f763-4b40-872c-794e841599ed
Genina, Anna
a33ea4b5-aaca-4108-bc90-e9bc8397cdf4
Gillams, Richard J.
89341fe4-db94-4d27-a5be-c092e2e8de5b
Lorenz, Christian D.
080b1193-25c1-49da-968a-ef522fdbec59
McLain, Sylvia E.
f0b6c048-e499-4eca-801e-359ac928f502
Steinke, Nicola
c5b12ef5-f763-4b40-872c-794e841599ed
Genina, Anna
a33ea4b5-aaca-4108-bc90-e9bc8397cdf4
Gillams, Richard J.
89341fe4-db94-4d27-a5be-c092e2e8de5b
Lorenz, Christian D.
080b1193-25c1-49da-968a-ef522fdbec59
McLain, Sylvia E.
f0b6c048-e499-4eca-801e-359ac928f502

Steinke, Nicola, Genina, Anna, Gillams, Richard J., Lorenz, Christian D. and McLain, Sylvia E. (2018) Proline and water stabilization of a universal two-step folding mechanism for β-turn formation in solution. Journal of the American Chemical Society, 140 (23), 7301-7312. (doi:10.1021/jacs.8b03643).

Record type: Article

Abstract

The atomic scale process by which proteins fold into their functional forms in aqueous solutions is still not well understood. While there is clearly an interplay between the sequence of the protein and the surrounding water solvent that leads to highly specific and reproducible folding in nature, there is still an ongoing debate concerning how water molecules aid in driving the folding process. By using a combination of techniques that provide information at the atomic level - neutron and X-ray diffraction and computer simulations - the mechanism of folding in a series of peptides that only vary with respect to the central side-chain residue has been determined. Specifically, β-turn formation for the KGXGK peptide (where X = P, G, S or L) occurs via a two-step water-driven attraction between specific sites on the peptide backbone. This proposed mechanism suggests that the site-specific hydration of the backbone facilitates the initial stages of protein folding and that this hydration interaction in combination with the presence of proline in the i + 1 position helps to stabilize the folded and intermediate folding state of the peptide in solution, leading to a greater propensity for PG containing sequences to occur in β-turns in proteins.

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More information

e-pub ahead of print date: 27 May 2018
Published date: 13 June 2018

Identifiers

Local EPrints ID: 434674
URI: http://eprints.soton.ac.uk/id/eprint/434674
ISSN: 0002-7863
PURE UUID: 50cf886e-3bd1-4f3e-9312-e016fcd7e753
ORCID for Richard J. Gillams: ORCID iD orcid.org/0000-0002-8597-8723

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Date deposited: 04 Oct 2019 16:30
Last modified: 07 Oct 2020 02:15

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Contributors

Author: Nicola Steinke
Author: Anna Genina
Author: Richard J. Gillams ORCID iD
Author: Christian D. Lorenz
Author: Sylvia E. McLain

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