Extended polypeptide linkers establish the spatial architecture of a pyruvate dehydrogenase multienzyme complex

Structure
Jeffrey S LengyelJacqueline L S Milne

Abstract

Icosahedral pyruvate dehydrogenase (PDH) enzyme complexes are molecular machines consisting of a central E2 core decorated by a shell of peripheral enzymes (E1 and E3) found localized at a distance of approximately 75-90 A from the core. Using a combination of biochemical, biophysical, and cryo-electron microscopic techniques, we show here that the gap between the E2 core and the shell of peripheral enzymes is maintained by the flexible but extended conformation adopted by 60 linker polypeptides that radiate outwards from the inner E2 core, irrespective of the E1 or E3 occupancy. The constancy of the gap is thus not due to protein-protein interactions in the outer protein shell. The extended nature of the E2 inner-linker regions thereby creates the restricted annular space in which the lipoyl domains of E2 that carry catalytic intermediates shuttle between E1, E2, and E3 active sites, while their conformational flexibility facilitates productive encounters.

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Citations

Aug 9, 2013·Bioscience, Biotechnology, and Biochemistry·Yuichi ShigeokaYoichi Aso
Oct 27, 2012·Hybridoma·Teerakul ArpornsuwanJohn C Wallace
Oct 1, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sowmini KumaranFrank Jordan
Oct 1, 2013·Bioconjugate Chemistry·Hanieh KhaliliSteve Brocchini
Feb 13, 2018·Nature Structural & Molecular Biology·Eviatar NatanSarah A Teichmann
Dec 13, 2019·Protein Engineering, Design & Selection : PEDS·Yuanyuan WangHu Tao
Jan 7, 2011·The Journal of Biological Chemistry·Bachar H Hassan, John E Cronan
Aug 28, 2020·Cell Communication and Signaling : CCS·Ioannis SkalidisPanagiotis L Kastritis
Jul 28, 2020·Biochimica Et Biophysica Acta. Biomembranes·Jean-Marc Jeckelmann, Bernhard Erni

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