Question

Characteristics of Lipid Transport Proteins Often when lipids are transported between different tissues, they are carried by proteins. In this exercise, you will explore the interactions between a lipid and a protein using the PDB (www.rcsb,org). Use the PDB identifier 2YG2 and study the structure of the complex between HDL-associated apolipoprotein \(\mathrm{M}\) and sphingosine-1-phosphate. Navigate to 3D View: Structure to answer the following questions. a. What protein motif is adopted by apolipoprotein M? b. Which amino acid residues do you find lining the sphingosine binding pocket? What do they have in common? c. The phosphoryl group of sphingosine-1-phosphate is exposed on the surface of the protein. Why do you suppose it is important that the transport protein binds the hydrocarbon tail of sphingosine-1-phosphate but not necessarily the polar head group?

Short answer

Apolipoprotein M adopts a helical motif. The binding pocket is lined with hydrophobic residues like Leu, Val, and Phe. The transport protein binds the hydrophobic tail to facilitate membrane interaction, leaving the polar head group exposed.

Step-by-step solution

Accessing the PDB Entry

Navigate to the RCSB Protein Data Bank website at www.rcsb.org and enter the PDB identifier '2YG2' in the search bar to access the structure of apolipoprotein M bound to sphingosine-1-phosphate.

Exploring the 3D Structure

Once you have accessed the entry for 2YG2, click on the '3D View: Structure' tab to visualize the molecular structure of the protein complex in three dimensions.

Identifying the Protein Motif

Observe the secondary structure elements in the apolipoprotein M. Apolipoprotein M primarily consists of helices organized in the form of a 'lipid-binding belt', indicating a helical motif.

Analyzing the Binding Pocket

Examine the binding pocket for sphingosine. Identify the amino acid residues lining the pocket by selecting the corresponding region in the 3D view. Common residues typically include hydrophobic side chains like leucine (Leu), valine (Val), and phenylalanine (Phe), which facilitate lipid interaction.

Evaluating the Importance of Hydrocarbon Interaction

The hydrocarbon tail of sphingosine-1-phosphate is buried within the protein, while the polar head group, including the phosphoryl group, is exposed to the solvent. This alignment makes it easier for the hydrophobic core region of cell membranes to interact with the lipid molecule during transport without the need for the transport protein to engage with the polar surface directly.

Key concepts

Apolipoprotein M

Apolipoprotein M (apoM) is a fascinating protein involved in lipid transport, crucial for maintaining various physiological functions. ApoM is primarily recognized for its presence in high-density lipoprotein (HDL), which is often dubbed the "good cholesterol." In the context of lipid transport, apoM adopts a specific structural motif known as a helix bundle or "lipid-binding belt," which allows it to engage lipids effectively.

This structure permits apoM to partially enclose lipids, facilitating their transport between different tissue sites. ApoM's effectiveness is largely due to its unique ability to form stable complexes with small lipid molecules. Each helix in this bundle stabilizes the interaction, ensuring that lipid molecules like sphingosine-1-phosphate are securely held.

• Participates in the regulation of endothelial cell function
• Plays a role in immune response and cell growth regulation
• Helix bundle structure enables efficient lipid transport

Sphingosine-1-Phosphate

Sphingosine-1-phosphate (S1P) is a potent bioactive lipid that plays a critical role in cellular signaling and lipid transport mechanisms. In the structure of the apoM-S1P complex, S1P acts as a cargo lipid that is specifically bound and transported by apoM.

The molecule comprises a hydrophobic tail and a polar head group. This dual nature is essential for its interactions within the protein environment and within cellular contexts. The role of S1P stretches across vascular biology, including angiogenesis and vascular maturation. Moreover, S1P influences immune cell trafficking and regulates inflammatory processes.

• Integral to maintaining vascular homeostasis
• Involved in critical endothelial barrier functions
• Regulates immune cell movement and responses

Protein-Lipid Interaction

Protein-lipid interactions are at the heart of lipid transport and are crucial for the functionality of proteins like apoM. In the apoM-S1P structure, these interactions are maximized due to the configuration of both the protein and the lipid molecule.

The interaction primarily occurs within a binding pocket that is lined with specific amino acid residues. These residues often include hydrophobic amino acids, which will be further discussed below, that facilitate a non-polar environment conducive to lipid binding. The intricate bonding stabilizes the lipid inside the protein, allowing for efficient transport.

• Hydrophobic interactions enhance binding stability
• Allows lipids to traverse aqueous environments effectively
• Enables selective binding of lipid molecules

Hydrophobic Amino Acids

Hydrophobic amino acids play a pivotal role in the lipid-binding function of proteins like apoM. In the context of the apoM-S1P complex, these amino acids line the binding pocket and include side chains from residues such as leucine (Leu), valine (Val), and phenylalanine (Phe).

These amino acids share a common characteristic—non-polar side chains—which create a hydrophobic environment inside the protein. This trait is advantageous as it drives the interaction with the hydrophobic tails of lipids like S1P, ensuring their secure attachment during transport.

• Leucine (Leu) and Valine (Val) provide bulky, non-polar environments
• Phenylalanine (Phe) contributes aromatic stability
• Facilitates lipid encapsulation and protection during transit

The interaction is further augmented by burying the hydrophobic lipid regions, shielding them from water, thereby maximizing the efficiency of lipid transport.