Characterization of Intersubunit Communication in the Virginiamycin trans-Acyl Transferase Polyketide Synthase

被引:38
作者
Dorival, Jonathan [1 ]
Annaval, Thibault [1 ]
Risser, Fanny [1 ]
Collin, Sabrina [1 ]
Roblin, Pierre [2 ,3 ]
Jacob, Christophe [1 ]
Gruez, Arnaud [1 ]
Chagot, Benjamin [1 ]
Weissman, Kira J. [1 ]
机构
[1] Biopole Univ Lorraine, Univ Lorraine, CNRS, Ingn Mol & Physiopathol Articulaire IMoPA,UMR 736, Campus Biol Sante,9 Ave Foret Haye,CS 50184, F-54505 Vandoeuvre Les Nancy, France
[2] Synchrotron SOLEIL, St Aubin BP 48, F-91192 Gif Sur Yvette, France
[3] INRA, Interact Assemblages BIA, Biopolymeres UR1268, Rue Geraudiere BP 71627, F-44316 Nantes 3, France
关键词
INTRINSICALLY DISORDERED PROTEINS; BIOLOGICAL MACROMOLECULES; QUANTITATIVE-ANALYSIS; SOLUTION SCATTERING; MOLECULAR-WEIGHT; DOCKING DOMAINS; NMR; BIOSYNTHESIS; SPECIFICITY; RESOLUTION;
D O I
10.1021/jacs.5b13372
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Modular polyketide synthases (PKSs) direct the biosynthesis of clinically valuable secondary metabolites in bacteria. The fidelity of chain growth depends on specific recognition between successive subunits in each assembly line: interactions mediated by C- and N-terminal "docking domains" (DDs). We have identified a new family of DDs in trans-acyl transferase PKSs, exemplified by a matched pair from the virginiamycin (Vir) system. In the absence of C-terminal partner (VirA (DD)-D-C) or a downstream catalytic domain, the N-terminal DD (VirFG (DD)-D-N) exhibits multiple characteristics of an intrinsically disordered protein. Fusion of the two docking domains results in a stable fold for VirFG NDD and an overall protein protein complex of unique topology whose structure we support by site-directed mutagenesis. Furthermore, using small-angle X-ray scattering (SAXS), the positions of the flanking acyl carrier protein and ketosynthase domains have been identified, allowing modeling of the complete intersubunit interface.
引用
收藏
页码:4155 / 4167
页数:13
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