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

• Published in: Biochimica et biophysica acta. Proteins and proteomics 2019-03, Vol.1867 (3), p.163-174
• Main Authors: Arya, Richa, Sharma, Bhaskar, Dhembla, Chetna, Pal, Ravi Kant, Patel, Ashok Kumar, Sundd, Monica, Ghosh, Biplab, Makde, Ravindra D., Kundu, Suman
• Format: Article
• Language: English
• Subjects: Acyl carrier protein; Apo-ACP; Fatty acid biosynthesis; Helix 2; Holo-ACP; Leishmania major
• ISSN: 1570-9639; 1878-1454
• DOI: 10.1016/j.bbapap.2018.12.001

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. [Display omitted] •Leishmania acyl carrier protein (LmACP) is dimer in apo-form, monomer in holo-form.•Phosphopantetheinylation of Ser37 may trigger the conversion from dimer to monomer.•Conformational changes in holo-LmACP dissociates LmACP-LmPPT interaction.•Rearrangement of helices 2 and 3 of LmACP widens the cavity of its holo-form.•Expanded holo-LmACP equips the protein for acyl chain accommodation.