Characterization of an acyl-coenzyme A binding protein predominantly expressed in human primitive progenitor cells

Abstract

Human acyl-coenzyme A binding domain-containing member 6 (ACBD6) is a modular protein that carries an acyl-CoA binding domain at its N terminus and two ankyrin motifs at its C terminus. ACBD6 binds long-chain acyl-CoAs with a strong preference for unsaturated, C18: 1-CoA and C20:4-CoA, over saturated, C16:0-CoA, acyl species. Deletion of the C terminus, which is not conserved among the members of this family, did not affect the binding capacity or the substrate specificity of the protein.

Probing the Interaction between the Coiled Coil Leucine Zipper of cGMP-dependent Protein Kinase Iα and the C Terminus of the Myosin Binding Subunit of the Myosin Light Chain Phosphatase

“…The hydrophobic residues that are conformationally affected upon complex formation, Leu 22 , Ile 33 , Leu 36 , and Leu 40 , are localized within the a/d hydrophobic core of the heptad repeat and are shared by both PKG-I␣ and PKG-I␤ supporting a structural role for these residues, a notion that has recently been supported by the extensive structural studies of GCN4 and LZ variants (52,53). In addition, the interaction interface of PKG-I␣ 1-59 ⅐MBS CT42 contains two charged lysines (Lys 37 and Lys 39 ) that are in the e and g positions of the fourth heptad repeat of PKG-I␣ 1-59 , respectively. Based on our structure (10) these lysines are partially exposed to the solvent extending out from the CC structure, which may permit them to form salt bridges with the Glu residues at g position in MBS.…”

“…SI4). Taken together, these data identify that residues Leu 22 , Leu 36 , Lys 37 , Leu 40 , Cys 43 , Gln 44 , Ile 54 , and Gly 55 are most affected by the interaction with MBS CT42 ; this suggests that these residues are either within close proximity to and/or involved in the formation of the interaction interface. These MBS CT42 interactions are within the intermediate exchange regime on the NMR time scale (Fig.…”

“…5C show the effective decrease in cross-peak intensity (highlighted in red). Based on these analyses, residues Leu 36 , Lys 37 , Leu 40 , Ile 54 , and Gly 55 support both chemical shift perturbation and peak intensity decreases, whereas residues Leu 22 , Cys 43 , and Gln 44 only support significantly decreased peak intensities. Chemical shift changes (Hz) and/or peak intensity (⌬I) decreases for residues Leu 22 , Leu 36 , Lys 37 , and Cys 43 have been plotted as two-dimensional contour plots overlaid with their one-dimensional traces to illustrate these perturbations (supplemental Fig.…”

Ligand binding to the ACBD6 protein regulates the acyl-CoA transferase reactions in membranes

“…The latter appears to be a gene duplication of ACBD1. Expression of the hACBD6 protein was found to be elevated in hemangioblasts of placental tissue, in cord blood, bone marrow hematopoietic progenitor cells, and circulating CD34 + cells, as well as erythrocyte precursors ( 25 ). ACBD6 mRNA levels were higher in hematopoietic progenitors as compared with lineage-committed cells ( 26,27 ).…”

“…Human ACBD6 is a modular protein with an N-terminal domain carrying the acyl-CoA binding domain and a carboxy-terminal domain with two ankyrin repeats, predicted to function as anchor motif to other proteins ( 25 ). This nonconserved C-terminus domain, present in members ACBD2 to ACBD6, is lacking in ACBD1 and ACBD7.…”