Journal article
Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins
Nature structural & molecular biology, Vol.25(3), pp.279-288
03/01/2018
DOI: 10.1038/s41594-018-0029-5
PMCID: PMC5995306
PMID: 29434345
Abstract
Cotranslational protein folding can facilitate rapid formation of functional structures. However, it can also cause premature assembly of protein complexes, if two interacting nascent chains are in close proximity. By analyzing known protein structures, we show that homomeric protein contacts are enriched toward the C termini of polypeptide chains across diverse proteomes. We hypothesize that this is the result of evolutionary constraints for folding to occur before assembly. Using high-throughput imaging of protein homomers in Escherichia coil and engineered protein constructs with N- and C-terminal oligomerization domains, we show that, indeed, proteins with C-terminal homomeric interface residues consistently assemble more efficiently than those with N- terminal interface residues. Using in vivo, in vitro and in silico experiments, we identify features that govern successful assembly of homomers, which have implications for protein design and expression optimization.
Details
- Title: Subtitle
- Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins
- Creators
- Eviatar Natan - The Aleph Lab Ltd, Oxford, UKTamaki Endoh - Konan UniversityLiora Haim-Vilmovsky - European Bioinformatics InstituteTilman Flock - MRC Laboratory of Molecular BiologyGuilhem Chalancon - MRC Laboratory of Molecular BiologyJonathan T. S. Hopper - Oxford Technologies (United Kingdom)Bilint Kintses - Hungarian Acad Sci, Synthet & Syst Biol Unit, Biol Res Ctr, Szeged, HungaryPeter Horvath - Institute for Molecular Medicine FinlandLejla Daruka - HUN-REN Szegedi Biológiai KutatóközpontGergely Fekete - HUN-REN Szegedi Biológiai KutatóközpontCsaba Pal - HUN-REN Szegedi Biológiai KutatóközpontBalazs Papp - HUN-REN Szegedi Biológiai KutatóközpontErika Oszi - Institute of Plant BiologyZoltan Magyar - Institute of Plant BiologyJoseph A. Marsh - Institute of Genetics and CancerAdrian H. Elcock - University of IowaM. Madan Babu - MRC Laboratory of Molecular BiologyCarol V. Robinson - University of OxfordNaoki Sugimoto - Konan UniversitySarah A. Teichmann - Wellcome Sanger Institute
- Resource Type
- Journal article
- Publication Details
- Nature structural & molecular biology, Vol.25(3), pp.279-288
- DOI
- 10.1038/s41594-018-0029-5
- PMID
- 29434345
- PMCID
- PMC5995306
- NLM abbreviation
- Nat Struct Mol Biol
- ISSN
- 1545-9993
- eISSN
- 1545-9985
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- National Brain Research Programme TEKES Finland Distinguished Professor Grant 120220 / NKFI; National Research, Development & Innovation Office (NRDIO) - Hungary Wellcome Trust; European Commission ISEF foundation ALTF 698-2012 / EMBO; European Molecular Biology Organization (EMBO) R01GM099865 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) EMBL Interdisciplinary Postdoctoral fellowship - H2020 Marie Sklodowska Curie Actions MC_U105185859 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission JP17H06351 / JSPS KAKENHI; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research (KAKENHI) ThPLAST 274192 / Directorate-General for Research and Innovation (FP7-PEOPLE-2010-IEF) MEXT; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) MCU105185859; MR/N020413/1 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission Ministry of Education, Culture, Sports, Science and Technology (ME5a-c); Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Boehringer Ingelheim Fond; Boehringer Ingelheim R01 GM099865 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Hirao Taro Foundation of KONAN GAKUEN for Academic Research MC_U105185859 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 'Lendulet' Programme of the Hungarian Academy of Sciences Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences; Hungarian Academy of Sciences MR/M02122X/1 / MRC Career Development Award; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
- Language
- English
- Date published
- 03/01/2018
- Academic Unit
- Physics and Astronomy; Biochemistry and Molecular Biology
- Record Identifier
- 9984288725102771
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