The apo-acyl coenzyme A binding protein of Leishmania major forms a unique 'AXXA' motif mediated dimer.

Autor: Verma S; National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India., Dangi RS; National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India., Rajak MK; National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India., Pal RK; National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India., Sundd M; National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India. Electronic address: monicasundd@nii.ac.in.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Proteins and proteomics [Biochim Biophys Acta Proteins Proteom] 2024 Jul 01; Vol. 1872 (4), pp. 141016. Date of Electronic Publication: 2024 Apr 12.
DOI: 10.1016/j.bbapap.2024.141016
Abstrakt: Acyl-Coenzyme A binding domain containing proteins (ACBDs) are ubiquitous in nearly all eukaryotes. They can exist as a free protein, or a domain of a large, multidomain, multifunctional protein. Besides modularity, ACBDs also display multiplicity. The same organism may have multiple ACBDs, differing in sequence and organization. By virtue of this diversity, ACBDs perform functions ranging from transport, synthesis, trafficking, signal transduction, transcription, and gene regulation. In plants and some microorganisms, these ACBDs are designated ACBPs (acyl-CoA binding proteins). The simplest ACBD/ACBP is a small, ∼10 kDa, soluble protein, comprising the acyl-CoA binding (ACB) domain. Most of these small ACBDs exist as monomers, while a few show a tendency to oligomerize. In sync with those studies, we report the crystal structure of two ACBDs from Leishmania major, named ACBP 103, and ACBP 96 based on the number of residues present. Interestingly, ACBP 103 crystallized as a monomer and a dimer under different crystallization conditions. Careful examination of the dimer disclosed an exposed 'AXXA' motif in the helix I of the two ACBP 103 monomers, aligned in a head-to-tail arrangement in the dimer. Glutaraldehyde cross-linking studies confirm that apo-ACBP 103 can self-associate in solution. Isothermal titration calorimetry studies further show that ACBP 103 can bind ligands ranging from C 8 - to C 20 -CoA, and the data could be best fit to a 'two sets of sites'/sequential binding site model. Taken together, our studies show that Leishmania major ACBP 103 can self-associate in the apo-form through a unique dimerization motif, an interaction that may play an important role in its function.
Competing Interests: Declaration of competing interest Monica Sundd reports financial support was provided by UGC-DAE CSR (Indore, India). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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