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DOI	10.1073/pnas.2102675118
	Efficient integration of transmembrane domains depends on the folding properties of the upstream sequences
	Janoschke M.; Zimmermann M.; Brunauer A.; Humbel R.; Junne T.; Spiess M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:33
英文摘要	The topology of most membrane proteins is defined by the successive integration of α-helical transmembrane domains at the Sec61 translocon. The translocon provides a pore for the transfer of polypeptide segments across the membrane while giving them lateral access to the lipid. For each polypeptide segment of ∼20 residues, the combined hydrophobicities of its constituent amino acids were previously shown to define the extent of membrane integration. Here, we discovered that different sequences preceding a potential transmembrane domain substantially affect its hydrophobicity requirement for integration. Rapidly folding domains, sequences that are intrinsically disordered or very short or capable of binding chaperones with high affinity, allow for efficient transmembrane integration with low-hydrophobicity thresholds for both orientations in the membrane. In contrast, long protein fragments, folding-deficient mutant domains, and artificial sequences not binding chaperones interfered with membrane integration, requiring higher hydrophobicity. We propose that the latter sequences, as they compact on their hydrophobic residues, partially folded but unable to reach a native state, expose hydrophobic surfaces that compete with the translocon for the emerging transmembrane segment, reducing integration efficiency. The results suggest that rapid folding or strong chaperone binding is required for efficient transmembrane integration. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Membrane proteins; Molecular chaperones; Protein folding; Sec61 translocon; Topogenesis
语种	英语
scopus关键词	chaperone; membrane protein; translocon; protein binding; Saccharomyces cerevisiae protein; amino acid sequence; Article; binding affinity; controlled study; cytoplasm; cytosol; hydrophobicity; mutant; nonhuman; protein domain; protein folding; protein protein interaction; Saccharomyces cerevisiae; amino acid sequence; gene expression regulation; genetics; immunoprecipitation; metabolism; protein domain; protein folding; Amino Acid Sequence; Cytoplasm; Gene Expression Regulation, Fungal; Immunoprecipitation; Molecular Chaperones; Protein Binding; Protein Domains; Protein Folding; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251075
作者单位	Biozentrum, University of Basel, Basel, 4056, Switzerland; Institute of Biophysics, Johannes Kepler University Linz, Linz, 4020, Austria
推荐引用方式 GB/T 7714	Janoschke M.,Zimmermann M.,Brunauer A.,et al. Efficient integration of transmembrane domains depends on the folding properties of the upstream sequences[J],2021,118(33).
APA	Janoschke M.,Zimmermann M.,Brunauer A.,Humbel R.,Junne T.,&Spiess M..(2021).Efficient integration of transmembrane domains depends on the folding properties of the upstream sequences.Proceedings of the National Academy of Sciences of the United States of America,118(33).
MLA	Janoschke M.,et al."Efficient integration of transmembrane domains depends on the folding properties of the upstream sequences".Proceedings of the National Academy of Sciences of the United States of America 118.33(2021).