Apolipophorin III: a lipid-triggered molecular switch

Area of Science:

• Biochemistry
• Insect Physiology
• Lipid Metabolism

Background:

• Apolipophorin III (apoLp-III) is crucial for neutral lipid transport in insects, particularly during flight.
• This exchangeable apolipoprotein exists in both lipid-free and lipid-bound states, with the latter being the active form.

Purpose of the Study:

• To investigate the functional similarity of apoLp-III from evolutionarily divergent insect species, Locusta migratoria and Manduca sexta.
• To understand the structural and interaction properties of apoLp-III in relation to lipid transport.

Main Methods:

• Comparative analysis of apoLp-III from L. migratoria and M. sexta.
• Studies involving model phospholipid vesicles and natural lipoproteins.
• Investigation of apoLp-III behavior under varying pH conditions.
• Utilizing NMR to determine the solution structure of M. sexta apoLp-III.

Main Results:

• ApoLp-III from both species interacts similarly with phospholipid vesicles, forming discoidal particles.
• Low intrinsic stability and acidic pH promote lipid binding by exposing hydrophobic surfaces and inducing molten globule-like structures.
• Recombinant apoLp-III proteins from both species can displace each other from lipophorin surfaces, indicating functional interchangeability.
• NMR structure reveals that M. sexta apoLp-III architecture closely parallels that of L. migratoria apoLp-III.

Conclusions:

• Despite differences in amino acid sequence and glycosylation, apoLp-III from L. migratoria and M. sexta exhibit remarkable functional conservation.
• The structural flexibility and interaction mechanisms of apoLp-III are key to its role in insect lipid transport.