Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops

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Standard

Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops. / Paslawski, Wojciech; Lillelund, Ove K; Kristensen, Julie Veje; Schafer, Nicholas P; Baker, Rosanna P; Urban, Sinisa; Otzen, Daniel E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 6, 10.02.2015, p. 7978-7983.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Paslawski, W, Lillelund, OK, Kristensen, JV, Schafer, NP, Baker, RP, Urban, S & Otzen, DE 2015, 'Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 6, pp. 7978-7983. https://doi.org/10.1073/pnas.1424751112

APA

Paslawski, W., Lillelund, O. K., Kristensen, J. V., Schafer, N. P., Baker, R. P., Urban, S., & Otzen, D. E. (2015). Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops. Proceedings of the National Academy of Sciences of the United States of America, 112(6), 7978-7983. https://doi.org/10.1073/pnas.1424751112

CBE

Paslawski W, Lillelund OK, Kristensen JV, Schafer NP, Baker RP, Urban S, Otzen DE. 2015. Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops. Proceedings of the National Academy of Sciences of the United States of America. 112(6):7978-7983. https://doi.org/10.1073/pnas.1424751112

MLA

Paslawski, Wojciech et al. "Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops". Proceedings of the National Academy of Sciences of the United States of America. 2015, 112(6). 7978-7983. https://doi.org/10.1073/pnas.1424751112

Vancouver

Paslawski W, Lillelund OK, Kristensen JV, Schafer NP, Baker RP, Urban S et al. Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops. Proceedings of the National Academy of Sciences of the United States of America. 2015 Feb 10;112(6):7978-7983. https://doi.org/10.1073/pnas.1424751112

Author

Paslawski, Wojciech ; Lillelund, Ove K ; Kristensen, Julie Veje ; Schafer, Nicholas P ; Baker, Rosanna P ; Urban, Sinisa ; Otzen, Daniel E. / Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 6. pp. 7978-7983.

Bibtex

@article{3d946c5ede2947f3a1fdf377b42ab651,
title = "Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops",
abstract = "Despite the ubiquity of helical membrane proteins in nature and their pharmacological importance, the mechanisms guiding their folding remain unclear. We performed kinetic folding and unfolding experiments on 69 mutants (engineered every 2-3 residues throughout the 178-residue transmembrane domain) of GlpG, a membrane-embedded rhomboid protease from Escherichia coli. The only clustering of significantly positive ϕ-values occurs at the cytosolic termini of transmembrane helices 1 and 2, which we identify as a compact nucleus. The three loops flanking these helices show a preponderance of negative ϕ-values, which are sometimes taken to be indicative of nonnative interactions in the transition state. Mutations in transmembrane helices 3-6 yielded predominantly ϕ-values near zero, indicating that this part of the protein has denatured-state-level structure in the transition state. We propose that loops 1-3 undergo conformational rearrangements to position the folding nucleus correctly, which then drives folding of the rest of the domain. A compact N-terminal nucleus is consistent with the vectorial nature of cotranslational membrane insertion found in vivo. The origin of the interactions in the transition state that lead to a large number of negative ϕ-values remains to be elucidated.",
author = "Wojciech Paslawski and Lillelund, {Ove K} and Kristensen, {Julie Veje} and Schafer, {Nicholas P} and Baker, {Rosanna P} and Sinisa Urban and Otzen, {Daniel E}",
year = "2015",
month = feb,
day = "10",
doi = "10.1073/pnas.1424751112",
language = "English",
volume = "112",
pages = "7978--7983",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "6",

}

RIS

TY - JOUR

T1 - Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops

AU - Paslawski, Wojciech

AU - Lillelund, Ove K

AU - Kristensen, Julie Veje

AU - Schafer, Nicholas P

AU - Baker, Rosanna P

AU - Urban, Sinisa

AU - Otzen, Daniel E

PY - 2015/2/10

Y1 - 2015/2/10

N2 - Despite the ubiquity of helical membrane proteins in nature and their pharmacological importance, the mechanisms guiding their folding remain unclear. We performed kinetic folding and unfolding experiments on 69 mutants (engineered every 2-3 residues throughout the 178-residue transmembrane domain) of GlpG, a membrane-embedded rhomboid protease from Escherichia coli. The only clustering of significantly positive ϕ-values occurs at the cytosolic termini of transmembrane helices 1 and 2, which we identify as a compact nucleus. The three loops flanking these helices show a preponderance of negative ϕ-values, which are sometimes taken to be indicative of nonnative interactions in the transition state. Mutations in transmembrane helices 3-6 yielded predominantly ϕ-values near zero, indicating that this part of the protein has denatured-state-level structure in the transition state. We propose that loops 1-3 undergo conformational rearrangements to position the folding nucleus correctly, which then drives folding of the rest of the domain. A compact N-terminal nucleus is consistent with the vectorial nature of cotranslational membrane insertion found in vivo. The origin of the interactions in the transition state that lead to a large number of negative ϕ-values remains to be elucidated.

AB - Despite the ubiquity of helical membrane proteins in nature and their pharmacological importance, the mechanisms guiding their folding remain unclear. We performed kinetic folding and unfolding experiments on 69 mutants (engineered every 2-3 residues throughout the 178-residue transmembrane domain) of GlpG, a membrane-embedded rhomboid protease from Escherichia coli. The only clustering of significantly positive ϕ-values occurs at the cytosolic termini of transmembrane helices 1 and 2, which we identify as a compact nucleus. The three loops flanking these helices show a preponderance of negative ϕ-values, which are sometimes taken to be indicative of nonnative interactions in the transition state. Mutations in transmembrane helices 3-6 yielded predominantly ϕ-values near zero, indicating that this part of the protein has denatured-state-level structure in the transition state. We propose that loops 1-3 undergo conformational rearrangements to position the folding nucleus correctly, which then drives folding of the rest of the domain. A compact N-terminal nucleus is consistent with the vectorial nature of cotranslational membrane insertion found in vivo. The origin of the interactions in the transition state that lead to a large number of negative ϕ-values remains to be elucidated.

UR - http://www.pnas.org/content/112/6.toc

U2 - 10.1073/pnas.1424751112

DO - 10.1073/pnas.1424751112

M3 - Journal article

C2 - 26056273

VL - 112

SP - 7978

EP - 7983

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 6

ER -