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Fold and function of polypeptide transport‐associated domains responsible for delivering unfolded proteins to membranes
Author(s) -
Knowles Timothy J.,
Jeeves Mark,
Bobat Saeeda,
Dancea Felician,
McClelland Darren,
Palmer Tracy,
Overduin Michael,
Henderson Ian R.
Publication year - 2008
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2008.06225.x
Subject(s) - periplasmic space , bacterial outer membrane , biology , membrane , porin , biophysics , transmembrane protein , protein folding , folding (dsp implementation) , membrane protein , membrane transport protein , biochemistry , crystallography , escherichia coli , chemistry , receptor , electrical engineering , gene , engineering
Summary Membranes of Gram‐negative bacteria, mitochondria and chloroplasts receive and fold β‐barrel transmembrane proteins through the action of po lypeptide t ransport‐ a ssociated (POTRA) domains. In Escherichia coli , folding substrates are inserted into the outer membrane by the essential protein YaeT, a prototypic Omp85 protein. Here, the articulation between tandem POTRA domains in solution is defined by nuclear magnetic resonance (NMR) spectroscopy, indicating an unprecedented juxtaposition. The novel solution orientations of all five POTRA domains are revealed by small‐angle X‐ray scattering of the entire 46 kDa periplasmic region. NMR titration studies show that strands from YaeT's canonical folding substrate, PhoE, bind non‐specifically along alternating sides of its mixed β sheets, thus providing an ideal platform for helping to fold nascent outer‐membrane proteins. Together, this provides the first structural model of how multiple POTRA domains recruit substrates from the periplasmic solution into the outer membrane.