Structure formation during co-translational folding of membrane proteins on the ribosome

Professor Paula Booth (primary)
King's College London
John Christodoulou (secondary)
Institute of Structural and Molecular Biology


Protein function is governed by the 3D structural fold, with health depending on the success of folding, and disease on its failure. Solving the question of how newly synthesised proteins fold to their functional states is considered as cracking the second half of the genetic code. However, most folding investigations target isolated, full length proteins, which is unrepresentative of cellular biosynthesis where proteins fold co-translationally as the ribosome is translating mRNA. This projects aims to probe co-translational folding of the understudied class of integral membrane proteins using high resolution NMR methods to elucidate the structure of the nascent protein.


1. Waudby, CA, Wlodarski, T, Karyadi, ME, Cassaignau, AME, Chan, SHS, Wentink, AS, . . . Christodoulou, J Systematic mapping of free energy landscapes of a growing filamin domain during biosynthesis Proc Natl Acad Sci U S A 2018 115 9744-9749
2. Cassaignau, AM, Launay, HM, Karyadi, ME, Wang, X, Waudby, CA, Deckert, A, . . . Cabrita, LD A strategy for co-translational folding studies of ribosome-bound nascent chain complexes using NMR spectroscopy Nature protocols 2016 11 1492-507
3. Harris, NJ, Reading, E, Ataka, K, Grzegorzewski, L, Charalambous, K, Liu, X, . . . Booth, PJ Structure formation during translocon-unassisted co-translational membrane protein folding Scientific reports 2017 7 8021
4. Urban, S;Shi, Y Core principles of intramembrane proteolysis: comparison of rhomboid and site-2 family proteases Curr Opin Struct Biol 2008 18 432-41
5. Reading, E, Hall, Z, Martens, C, Haghighi, T, Findlay, H, Ahdash, Z, . . . Booth, PJ Interrogating Membrane Protein Conformational Dynamics within Native Lipid Compositions Angew Chem Int Ed Engl 2017 56 15654-15657

Molecules, cells and industrial biotechnology
Area of Biology
Chemical BiologyStructural Biology
Techniques & Approaches
BiochemistryBiophysicsChemistryMolecular Biology