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DC Field | Value | Language |
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dc.contributor.author | Vijayakrishnan, S | - |
dc.contributor.author | Callow, P | - |
dc.contributor.author | Nutley, MA | - |
dc.contributor.author | McGow, DP | - |
dc.contributor.author | Gilbert, D | - |
dc.contributor.author | Kropholler, P | - |
dc.contributor.author | Cooper, A | - |
dc.contributor.author | Byron, O | - |
dc.contributor.author | Lindsay, JG | - |
dc.date.accessioned | 2012-06-01T10:39:31Z | - |
dc.date.available | 2012-06-01T10:39:31Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Biochemical Journal, 437: 565-574, 2011 | en_US |
dc.identifier.issn | 0264-6021 | - |
dc.identifier.uri | http://www.biochemj.org/bj/437/bj4370565.htm | en |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/6461 | - |
dc.description | The final version of this article is available at the link below. | en_US |
dc.description.abstract | Crucial to glucose homoeostasis in humans, the hPDC (human pyruvate dehydrogenase complex) is a massive molecular machine comprising multiple copies of three distinct enzymes (E1–E3) and an accessory subunit, E3BP (E3-binding protein). Its icosahedral E2/E3BP 60-meric ‘core’ provides the central structural and mechanistic framework ensuring favourable E1 and E3 positioning and enzyme co-operativity. Current core models indicate either a 48E2+12E3BP or a 40E2+20E3BP subunit composition. In the present study, we demonstrate clear differences in subunit content and organization between the recombinant hPDC core (rhPDC; 40E2+20E3BP), generated under defined conditions where E3BP is produced in excess, and its native bovine (48E2+12E3BP) counterpart. The results of the present study provide a rational basis for resolving apparent differences between previous models, both obtained using rhE2/E3BP core assemblies where no account was taken of relative E2 and E3BP expression levels. Mathematical modelling predicts that an ‘average’ 48E2+12E3BP core arrangement allows maximum flexibility in assembly, while providing the appropriate balance of bound E1 and E3 enzymes for optimal catalytic efficiency and regulatory fine-tuning. We also show that the rhE2/E3BP and bovine E2/E3BP cores bind E3s with a 2:1 stoichiometry, and propose that mammalian PDC comprises a heterogeneous population of assemblies incorporating a network of E3 (and possibly E1) cross-bridges above the core surface. | en_US |
dc.description.sponsorship | This work was partly supported by EPSRC (under grants GR/R99393/01 and EP/C015452/1). | en_US |
dc.language.iso | en | en_US |
dc.publisher | Biochemical Society | en_US |
dc.subject | E3-binding stoichiometry | en_US |
dc.subject | E2/E3BP core organization | en_US |
dc.subject | Isothermal titration calorimetry (ITC) | en_US |
dc.subject | Pyruvate dehydrogenase complex | en_US |
dc.subject | Small-angle neutron scattering (SANS) | en_US |
dc.subject | Variable substitution model | en_US |
dc.title | Variation in the organization and subunit composition of the mammalian pyruvate dehydrogenase complex E2/E3BP core assembly | en_US |
dc.type | Article | en_US |
dc.identifier.doi | http://dx.doi.org/10.1042/BJ20101784 | - |
pubs.organisational-data | /Brunel | - |
pubs.organisational-data | /Brunel/Brunel (Active) | - |
pubs.organisational-data | /Brunel/Brunel (Active)/School of Info. Systems, Comp & Maths | - |
pubs.organisational-data | /Brunel/Research Centres (RG) | - |
pubs.organisational-data | /Brunel/Research Centres (RG)/CIKM | - |
pubs.organisational-data | /Brunel/School of Information Systems, Computing and Mathematics (RG) | - |
pubs.organisational-data | /Brunel/School of Information Systems, Computing and Mathematics (RG)/CIKM | - |
Appears in Collections: | Publications Computer Science Dept of Computer Science Research Papers |
Files in This Item:
File | Description | Size | Format | |
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VijayakrishnanFINAL.pdf | 860.76 kB | Adobe PDF | View/Open |
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