Solution Structure of the Tandem Acyl Carrier Protein Domains from a Polyunsaturated Fatty Acid Synthase Reveals Beads-on-a-String Configuration
Stagg, Loren J.
Vassallo, David A.
Vega, Irving E.
Arold, Stefan T.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
Structural Biology and Engineering
Permanent link to this recordhttp://hdl.handle.net/10754/325312
MetadataShow full item record
AbstractThe polyunsaturated fatty acid (PUFA) synthases from deep-sea bacteria invariably contain multiple acyl carrier protein (ACP) domains in tandem. This conserved tandem arrangement has been implicated in both amplification of fatty acid production (additive effect) and in structural stabilization of the multidomain protein (synergistic effect). While the more accepted model is one in which domains act independently, recent reports suggest that ACP domains may form higher oligomers. Elucidating the three-dimensional structure of tandem arrangements may therefore give important insights into the functional relevance of these structures, and hence guide bioengineering strategies. In an effort to elucidate the three-dimensional structure of tandem repeats from deep-sea anaerobic bacteria, we have expressed and purified a fragment consisting of five tandem ACP domains from the PUFA synthase from Photobacterium profundum. Analysis of the tandem ACP fragment by analytical gel filtration chromatography showed a retention time suggestive of a multimeric protein. However, small angle X-ray scattering (SAXS) revealed that the multi-ACP fragment is an elongated monomer which does not form a globular unit. Stokes radii calculated from atomic monomeric SAXS models were comparable to those measured by analytical gel filtration chromatography, showing that in the gel filtration experiment, the molecular weight was overestimated due to the elongated protein shape. Thermal denaturation monitored by circular dichroism showed that unfolding of the tandem construct was not cooperative, and that the tandem arrangement did not stabilize the protein. Taken together, these data are consistent with an elongated beads-on-a-string arrangement of the tandem ACP domains in PUFA synthases, and speak against synergistic biocatalytic effects promoted by quaternary structuring. Thus, it is possible to envision bioengineering strategies which simply involve the artificial linking of multiple ACP domains for increasing the yield of fatty acids in bacterial cultures. 2013 Trujillo et al.
CitationTrujillo U, Vázquez-Rosa E, Oyola-Robles D, Stagg LJ, Vassallo DA, et al. (2013) Solution Structure of the Tandem Acyl Carrier Protein Domains from a Polyunsaturated Fatty Acid Synthase Reveals Beads-on-a-String Configuration. PLoS ONE 8: e57859. doi:10.1371/journal.pone.0057859.
PublisherPublic Library of Science (PLoS)
PubMed Central IDPMC3585217
- Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli.
- Authors: Oyola-Robles D, Rullán-Lind C, Carballeira NM, Baerga-Ortiz A
- Issue date: 2014 Feb 5
- Artificial covalent linkage of bacterial acyl carrier proteins for fatty acid production.
- Authors: Rullán-Lind C, Ortiz-Rosario M, García-González A, Stojanoff V, Chorna NE, Pietri RB, Baerga-Ortiz A
- Issue date: 2019 Nov 5
- Loading of malonyl-CoA onto tandem acyl carrier protein domains of polyunsaturated fatty acid synthases.
- Authors: Santín O, Moncalián G
- Issue date: 2018 Aug 10
- Tandem acyl carrier protein domains in polyunsaturated fatty acid synthases.
- Authors: Jiang H, Rajski SR, Shen B
- Issue date: 2009
- Conserved secondary structure in the actinorhodin polyketide synthase acyl carrier protein from Streptomyces coelicolor A3(2) and the fatty acid synthase acyl carrier protein from Escherichia coli.
- Authors: Crump MP, Crosby J, Dempsey CE, Murray M, Hopwood DA, Simpson TJ
- Issue date: 1996 Aug 12
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