Probing the C-terminal domain of lipid-free apoA-I demonstrates the vital role of the H10B sequence repeat in HDL formation

Mei, Xiaohu; Liu, Mingjing; Herscovitz, Haya; Atkinson, David

doi:10.1194/jlr.m068874

Cited by 20 publications

(21 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More likely, GPR ApoLP domains fold into specific 3D shapes. The ApoLP structure is very dynamic, and monomers fold as bundles of helices or extended curved structures in the presence of lipids (44,45). ApoLPs form two types of complexes of ∼9-10 nm diameter when associated with lipids: (i) three ApoLPs arranged in a trefoil with their alpha helical regions on the surface of lipid spheres or (ii) two stacked ApoLPs around a lipid disk (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

GROWTH POLE RING protein forms a 200-nm-diameter ring structure essential for polar growth and rod shape in Agrobacterium tumefaciens

Zupan

Grangeon

Robalino-Espinosa

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Polar growth in Agrobacterium pirates and repurposes well-known bacterial cell cycle proteins, such as FtsZ, FtsA, PopZ, and PodJ. Here we identify a heretofore unknown protein that we name GROWTH POLE RING (GPR) due to its striking localization as a hexameric ring at the growth pole during polar growth. GPR also localizes at the midcell late in the cell cycle just before division, where it is then poised to be precisely localized at new growth poles in sibling cells. GPR is 2,115 aa long, with two N-terminal transmembrane domains placing the bulk of the protein in the cytoplasm, N-and C-terminal proline-rich disordered regions, and a large 1,700-aa central region of continuous α-helical domains. This latter region contains 12 predicted adjacent or overlapping apolipoprotein domains that may function to sequester lipids during polar growth. Stable genetic deletion or riboswitch-controlled depletion results in spherical cells that grow poorly; thus, GPR is essential for wild-type growth and morphology. As GPR has no predicted enzymatic domains and it forms a distinct 200-nm-diameter ring, we propose that GPR is a structural component of an organizing center for peptidoglycan and membrane syntheses critical for cell envelope formation during polar growth. GPR homologs are found in numerous Rhizobiales; thus, our results and proposed model are fundamental to understanding polar growth strategy in a variety of bacterial species.Agrobacterium | bacterial polar growth | apolipoprotein | rod-shape morphology | GROWTH POLE RING protein

show abstract

Section: Discussionmentioning

confidence: 99%

GROWTH POLE RING protein forms a 200-nm-diameter ring structure essential for polar growth and rod shape in Agrobacterium tumefaciens

Zupan

Grangeon

Robalino-Espinosa

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…ApoA-I proteins were expressed and purified as described previously (15,29). For ABCA1 purification, HEK293F cells were grown in Freestyle Expression medium (Invitrogen) in 1 liter rotating flasks at 130 rpm, 8% CO 2 , 37°C.…”

Section: Abca1 and Apoa-i Purificationmentioning

confidence: 99%

N-terminal mutation of apoA-I and interaction with ABCA1 reveal mechanisms of nascent HDL biogenesis

Liu

Mei

Herscovitz

et al. 2019

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

“…Phillips and colleagues proposed that the C-terminus in full length apoA1 interacts with lipid and transmits a structural change allowing the unfolding of apoA1's helical bundle revealing its detergent-like activities [13,14]. This model and a similar one from Atkinson and colleagues [6,15] can explain why the ΔC is defective in lipid binding, which is recovered by the ΔN/C isoform. We previously demonstrated that the free energy required for guanidine unfolding of apoA1 isoforms is ranked ΔC > WT > ΔN/C > ΔN [16].…”

Section: Introductionmentioning

confidence: 98%

First eight residues of apolipoprotein A-I mediate the C-terminus control of helical bundle unfolding and its lipidation

et al. 2020

View full text Add to dashboard Cite

The crystal structure of a C-terminal deletion of apolipoprotein A-I (apoA1) shows a large helical bundle structure in the amino half of the protein, from residues 8 to 115. Using site directed mutagenesis, guanidine or thermal denaturation, cell free liposome clearance, and cellular ABCA1-mediated cholesterol efflux assays, we demonstrate that apoA1 lipidation can occur when the thermodynamic barrier to this bundle unfolding is lowered. The absence of the C-terminus renders the bundle harder to unfold resulting in loss of apoA1 lipidation that can be reversed by point mutations, such as Trp8Ala, and by truncations as short as 8 residues in the amino terminus, both of which facilitate helical bundle unfolding. Locking the bundle via a disulfide bond leads to loss of apoA1 lipidation. We propose a model in which the C-terminus acts on the N-terminus to destabilize this helical bundle. Upon lipid binding to the C-terminus, Trp8 is displaced from its interaction with Phe57, Arg61, Leu64, Val67, Phe71, and Trp72 to destabilize the bundle. However, when the C-terminus is deleted, Trp8 cannot be displaced, the bundle cannot unfold, and apoA1 cannot be lipidated.

show abstract

Probing the C-terminal domain of lipid-free apoA-I demonstrates the vital role of the H10B sequence repeat in HDL formation

Cited by 20 publications

References 53 publications

GROWTH POLE RING protein forms a 200-nm-diameter ring structure essential for polar growth and rod shape in Agrobacterium tumefaciens

GROWTH POLE RING protein forms a 200-nm-diameter ring structure essential for polar growth and rod shape in Agrobacterium tumefaciens

N-terminal mutation of apoA-I and interaction with ABCA1 reveal mechanisms of nascent HDL biogenesis

First eight residues of apolipoprotein A-I mediate the C-terminus control of helical bundle unfolding and its lipidation

Contact Info

Product

Resources

About