Probing the 121–136 Domain of Lecithin:Cholesterol Acyltransferase Using Antibodies

Murray, Karen Riva; Nair, Maya; Ayyobi, Amir F; Hill, John S.; Pritchard, P H; Lacko, Andras G.

doi:10.1006/abbi.2000.2154

Cited by 9 publications

(10 citation statements)

References 30 publications

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“…Another substitution in this region, the mutant Thr 123 to Ile was also reported to be inactive with HDL [29,30]. Murray et al found that amino acids at positions 121 to 136 of LCAT were highly conserved among six different species and that LCAT activity is sensitive to mutations in this region [31]. They explored this observation by measuring antibody binding to this region when LCAT was bound to a hydrophobic surface or to plasma HDL coated onto microtiter plates.…”

Section: Structure Of Lcatmentioning

confidence: 99%

“…They explored this observation by measuring antibody binding to this region when LCAT was bound to a hydrophobic surface or to plasma HDL coated onto microtiter plates. They found that the amino acid region at position 121 to 136 is unavailable for binding a polyclonal antibody specific for this region [31] when LCAT is bound to lipid. Based on predictions that the amino acid region at position 154–171 of LCAT could form an amphiphthic α-helix, Peelman et al demonstrated that the synthetic peptide had a strong affinity for phospholipids [32].…”

Section: Structure Of Lcatmentioning

confidence: 99%

“…The conformation of LCAT depicted in Figure 1 was derived from a model containing amino acids at position 9 through position 420 of the mature protein [52]. Figure 1B illustrates that after LCAT docks or binds to ApoA-I helix 6 (purple), the LCAT domain corresponding to amino acids at positions 121–136 (blue) are shielded and are no longer accessible, as suggested by Murray et al , owing to their interaction with the surface of the rHDL [31]. LCAT belongs to the α/β hydrolase fold family and there is a ‘gate or lid’ that may be involved in controlling substrate specificity.…”

Section: Lcat Is Required For Hdl Maturationmentioning

confidence: 99%

“…Helix 6 residues in the center of this region, amino acids at position 143–164, are shown in purple, while all other ApoA-I amino acids are shown in green. Murray et al suggested that the LCAT region corresponding to amino acids at position 121 to 136, highlighted in blue (A) , was shielded when LCAT binds lipid [31]. An arrow points to this region.…”

Section: Figurementioning

confidence: 99%

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Activation of lecithin: cholesterol acyltransferase by HDL ApoA-I central helices

Sorci‐Thomas

Bhat

Thomas

2009

Clinical Lipidology

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Lecithin:cholesterol acyltransferase (LCAT) is an enzyme that first hydrolyzes the sn-2 position of phospholipids, preferentially a diacylphosphocholine, and then transfers the fatty acid to cholesterol to yield a cholesteryl ester. HDL ApoA-I is the principal catalytic activator for LCAT. Activity of LCAT on nascent or lipid-poor HDL particles composed of phospholipid, cholesterol and ApoA-I allows the maturation of HDL particles into lipid-rich spherical particles that contain a core of cholesteryl ester surrounded by phospholipid and ApoA-I on the surface. This article reviews the recent progress in elucidating structural aspects of the interaction between LCAT and ApoA-I. In the last decade, there has been considerable progress in understanding the structure of ApoA-I and the central helices 5, 6, and 7 that are known to activate LCAT. However, much less information has been forthcoming describing the 3D structure and conformation of LCAT required to catalyze two separate reactions within a single monomeric peptide.

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Section: Structure Of Lcatmentioning

confidence: 99%

Section: Structure Of Lcatmentioning

confidence: 99%

Section: Lcat Is Required For Hdl Maturationmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Activation of lecithin: cholesterol acyltransferase by HDL ApoA-I central helices

Sorci‐Thomas

Bhat

Thomas

2009

Clinical Lipidology

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“…Such antibodies have been used to discriminate between the inactive and active conformations of a protein [72], to neutralize viruses [73] and to differentiate between the aggregated or monomeric form of proteins [74][75][76]. When proteins are adsorbed on material surfaces, some epitopes are masked, which reduces the binding of the corresponding antibodies [77][78][79]. Conversely, some internal protein epitopes may become exposed upon adsorption onto material surfaces, which increases the binding of the corresponding antibodies [80].…”

Section: Evidences Of Material-induced Protein Conformational Changesmentioning

confidence: 99%

Protein conformational changes induced by adsorption onto material surfaces: an important issue for biomedical applications of material science

Ballet¹,

Boulangé²,

Bréchet³

et al. 2010

Bulletin of the Polish Academy of Sciences: Technical Sciences

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Abstract. Protein adsorption on solid surfaces is a widespread phenomenon of large biological and biotechnological significance. Conformational changes are likely to accompany protein adsorption, but are difficult to evidence directly. Nevertheless they have important consequences, since the partial unfolding of protein domains can expose hitherto hidden amino acids. This remodeling of the protein surface can trigger the activation of molecular complexes such as the blood coagulation cascade or the innate immune complement system. In the case of extracellular matrix, it can also change the way cells interact with the material surfaces and result in modified cell behavior. In this review, we present direct and indirect evidences that support the view that some proteins change their conformation upon adsorption. We also show that both physical and chemical methods are needed to study the extent and kinetics of protein conformational changes. In particular, AFM techniques and cryo-electron microscopy provide useful and complementary information. We then review the chemical and topological features of both proteins and material surfaces in relation with protein adsorption. Mutating key amino acids in proteins changes their stability and this is related to material-induced conformational changes, as shown for instance with insulin. In addition, combinatorial methods should provide valuable information about peptide or antibody adsorption on well-defined material surfaces. These techniques could be combined with molecular modeling methods to decipher the rules governing conformational changes associated with protein adsorption.

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Binding of 8-anilino-1-naphthalenesulfonate to lecithin:cholesterol acyltransferase studied by fluorescence techniques

Sarkar

Bharill

Gryczyński

et al. 2008

Journal of Photochemistry and Photobiology B: Biology

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Probing the 121–136 Domain of Lecithin:Cholesterol Acyltransferase Using Antibodies

Cited by 9 publications

References 30 publications

Activation of lecithin: cholesterol acyltransferase by HDL ApoA-I central helices

Activation of lecithin: cholesterol acyltransferase by HDL ApoA-I central helices

Protein conformational changes induced by adsorption onto material surfaces: an important issue for biomedical applications of material science

Binding of 8-anilino-1-naphthalenesulfonate to lecithin:cholesterol acyltransferase studied by fluorescence techniques

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