Fatty-acid-binding protein from the flight muscle of Locusta migratoria

Evolutionary variations in fatty acid binding

Christian Lücke, Ye Qiao, Herman T B Van Moerkerk, Jacques H. Veerkamp, James A. Hamilton

Research output: Contribution to journalArticle

Abstract

Intracellular lipid-binding proteins have evolved from a common ancestral gene with the appearance of mitochondrial oxidation, to guarantee, for example, transport of fatty acids through the aqueous cytosol to their site of utilization. The mammalian forms of these lipid carriers are structurally well-characterized and have been categorized, on the basis of sequence similarities and several typical ligand-binding features, into four subfamilies. Only a single complex structure of an invertebrate fatty-acid-binding protein (FABP) has been reported to date, which reveals a unique ligand-binding arrangement yet unknown in vertebrate FABPs. In the present study, the structure of a second invertebrate FABP (locust muscle) complexed with a fatty acid has been determined on the basis of intermolecular NOE connectivities between the protein and the uniformly 13C-enriched oleate ligand. The resulting ligand conformation, although resembling the closely related mammalian heart- and adipocyte-type FABPs, is characterized by certain binding features that differ significantly from the typical hairpin-turn ligand shapes of the latter forms. This is primarily due to an alanine-to-leucine substitution in locust FABPs that produces a steric hindrance for ligand binding, A comparison with an FABP from tobacco hornworm larvae furthermore demonstrates that certain amino acid substitutions that appear to be specific for invertebrates decidedly influence the binding arrangement inside the protein cavity. Hence, as a result of these evolutionary variations, invertebrate FABPs may display a much greater diversity in intracellular lipid binding than observed for the mammalian transport proteins, thus possibly providing new insights for the design of modified lipid carriers.

Original languageEnglish (US)
Pages (from-to)6296-6305
Number of pages10
JournalBiochemistry®
Volume45
Issue number20
DOIs
StatePublished - May 23 2006
Externally publishedYes

Fingerprint

Locusta migratoria
Fatty Acid-Binding Proteins
Muscle
Fatty Acids
Invertebrates
Ligands
Muscles
Lipids
Grasshoppers
Carrier Proteins
Substitution reactions
Manduca
Tobacco
Amino Acid Substitution
Oleic Acid
Adipocytes
Leucine
Alanine
Cytosol
Larva

ASJC Scopus subject areas

  • Biochemistry

Cite this

Fatty-acid-binding protein from the flight muscle of Locusta migratoria : Evolutionary variations in fatty acid binding. / Lücke, Christian; Qiao, Ye; Van Moerkerk, Herman T B; Veerkamp, Jacques H.; Hamilton, James A.

In: Biochemistry®, Vol. 45, No. 20, 23.05.2006, p. 6296-6305.

Research output: Contribution to journalArticle

Lücke, Christian ; Qiao, Ye ; Van Moerkerk, Herman T B ; Veerkamp, Jacques H. ; Hamilton, James A. / Fatty-acid-binding protein from the flight muscle of Locusta migratoria : Evolutionary variations in fatty acid binding. In: Biochemistry®. 2006 ; Vol. 45, No. 20. pp. 6296-6305.
@article{369cad55ac934a0dae87989daeb4b648,
title = "Fatty-acid-binding protein from the flight muscle of Locusta migratoria: Evolutionary variations in fatty acid binding",
abstract = "Intracellular lipid-binding proteins have evolved from a common ancestral gene with the appearance of mitochondrial oxidation, to guarantee, for example, transport of fatty acids through the aqueous cytosol to their site of utilization. The mammalian forms of these lipid carriers are structurally well-characterized and have been categorized, on the basis of sequence similarities and several typical ligand-binding features, into four subfamilies. Only a single complex structure of an invertebrate fatty-acid-binding protein (FABP) has been reported to date, which reveals a unique ligand-binding arrangement yet unknown in vertebrate FABPs. In the present study, the structure of a second invertebrate FABP (locust muscle) complexed with a fatty acid has been determined on the basis of intermolecular NOE connectivities between the protein and the uniformly 13C-enriched oleate ligand. The resulting ligand conformation, although resembling the closely related mammalian heart- and adipocyte-type FABPs, is characterized by certain binding features that differ significantly from the typical hairpin-turn ligand shapes of the latter forms. This is primarily due to an alanine-to-leucine substitution in locust FABPs that produces a steric hindrance for ligand binding, A comparison with an FABP from tobacco hornworm larvae furthermore demonstrates that certain amino acid substitutions that appear to be specific for invertebrates decidedly influence the binding arrangement inside the protein cavity. Hence, as a result of these evolutionary variations, invertebrate FABPs may display a much greater diversity in intracellular lipid binding than observed for the mammalian transport proteins, thus possibly providing new insights for the design of modified lipid carriers.",
author = "Christian L{\"u}cke and Ye Qiao and {Van Moerkerk}, {Herman T B} and Veerkamp, {Jacques H.} and Hamilton, {James A.}",
year = "2006",
month = "5",
day = "23",
doi = "10.1021/bi060224f",
language = "English (US)",
volume = "45",
pages = "6296--6305",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "20",

}

TY - JOUR

T1 - Fatty-acid-binding protein from the flight muscle of Locusta migratoria

T2 - Evolutionary variations in fatty acid binding

AU - Lücke, Christian

AU - Qiao, Ye

AU - Van Moerkerk, Herman T B

AU - Veerkamp, Jacques H.

AU - Hamilton, James A.

PY - 2006/5/23

Y1 - 2006/5/23

N2 - Intracellular lipid-binding proteins have evolved from a common ancestral gene with the appearance of mitochondrial oxidation, to guarantee, for example, transport of fatty acids through the aqueous cytosol to their site of utilization. The mammalian forms of these lipid carriers are structurally well-characterized and have been categorized, on the basis of sequence similarities and several typical ligand-binding features, into four subfamilies. Only a single complex structure of an invertebrate fatty-acid-binding protein (FABP) has been reported to date, which reveals a unique ligand-binding arrangement yet unknown in vertebrate FABPs. In the present study, the structure of a second invertebrate FABP (locust muscle) complexed with a fatty acid has been determined on the basis of intermolecular NOE connectivities between the protein and the uniformly 13C-enriched oleate ligand. The resulting ligand conformation, although resembling the closely related mammalian heart- and adipocyte-type FABPs, is characterized by certain binding features that differ significantly from the typical hairpin-turn ligand shapes of the latter forms. This is primarily due to an alanine-to-leucine substitution in locust FABPs that produces a steric hindrance for ligand binding, A comparison with an FABP from tobacco hornworm larvae furthermore demonstrates that certain amino acid substitutions that appear to be specific for invertebrates decidedly influence the binding arrangement inside the protein cavity. Hence, as a result of these evolutionary variations, invertebrate FABPs may display a much greater diversity in intracellular lipid binding than observed for the mammalian transport proteins, thus possibly providing new insights for the design of modified lipid carriers.

AB - Intracellular lipid-binding proteins have evolved from a common ancestral gene with the appearance of mitochondrial oxidation, to guarantee, for example, transport of fatty acids through the aqueous cytosol to their site of utilization. The mammalian forms of these lipid carriers are structurally well-characterized and have been categorized, on the basis of sequence similarities and several typical ligand-binding features, into four subfamilies. Only a single complex structure of an invertebrate fatty-acid-binding protein (FABP) has been reported to date, which reveals a unique ligand-binding arrangement yet unknown in vertebrate FABPs. In the present study, the structure of a second invertebrate FABP (locust muscle) complexed with a fatty acid has been determined on the basis of intermolecular NOE connectivities between the protein and the uniformly 13C-enriched oleate ligand. The resulting ligand conformation, although resembling the closely related mammalian heart- and adipocyte-type FABPs, is characterized by certain binding features that differ significantly from the typical hairpin-turn ligand shapes of the latter forms. This is primarily due to an alanine-to-leucine substitution in locust FABPs that produces a steric hindrance for ligand binding, A comparison with an FABP from tobacco hornworm larvae furthermore demonstrates that certain amino acid substitutions that appear to be specific for invertebrates decidedly influence the binding arrangement inside the protein cavity. Hence, as a result of these evolutionary variations, invertebrate FABPs may display a much greater diversity in intracellular lipid binding than observed for the mammalian transport proteins, thus possibly providing new insights for the design of modified lipid carriers.

UR - http://www.scopus.com/inward/record.url?scp=33646891301&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646891301&partnerID=8YFLogxK

U2 - 10.1021/bi060224f

DO - 10.1021/bi060224f

M3 - Article

VL - 45

SP - 6296

EP - 6305

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 20

ER -