A conformational switch from a closed apo- to an open holo-form equips the acyl carrier protein for acyl chain accommodation.

Authors:
Richa Arya
Richa Arya
Banaras Hindu University
India
Bhaskar Sharma
Bhaskar Sharma
Indian Veterinary Research Institute
Bareilly | India
Ravi Kant Pal
Ravi Kant Pal
National Institute of Immunology
India
Ashok Kumar Patel
Ashok Kumar Patel
Banaras Hindu University
India
Monica Sundd
Monica Sundd
National Institute of Immunology
India
Biplab Ghosh
Biplab Ghosh
Banaras Hindu University
India
Ravindra D Makde
Ravindra D Makde
University Park
United States

Biochim Biophys Acta Proteins Proteom 2019 Mar 10;1867(3):163-174. Epub 2018 Dec 10.

Department of Biochemistry, University of Delhi South Campus, New Delhi 110021, India. Electronic address:

Acyl carrier proteins (ACPs) play crucial roles in the biosynthesis of fatty acids, non-ribosomal polypeptides and polyketides. The three-dimensional NMR structure of Leishmania major holo-LmACP, belonging to the type II pathway, has been reported previously, but the structure of its apo-form and its conformational differences with the holo-form remain to be explored. Here we report the crystal structures of apo-LmACP (wild-type and S37A mutant) at 2.0 Å resolution and compare their key features with the structures of holo-LmACP (wild-type) and other type II ACPs from Escherichia coli and Plasmodium falciparum. The crystal structure of apo-LmACP, which is homologous to other type II ACPs, displays some key structural rearrangements as compared to its holo-structure. Contrary to holo-form, which exists predominantly as a monomer, the apo-form exists as a mixture of monomeric and dimeric population in solution. In contrast to the closed structure of apo-LmACP, holo-LmACP structure was observed in an open conformation as a result of reorganization of specific helices and loops. We propose that the structural changes exhibited by LmACP occur due to the attachment of the phosphopantetheine arm and may be a prerequisite for the initiation of fatty acid synthesis. The movement of helix 3 may also play a role in the dissociation of holo-LmACP from its cognate enzymes of the FAS II pathway.

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Source
http://dx.doi.org/10.1016/j.bbapap.2018.12.001DOI Listing
March 2019
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