Partitioning of Amino Acid Side Chains into Lipid Bilayers: Results from Computer Simulations and Comparison to Experiment

摘要

The free energy of partitioning an amino acid side chain from water into the cell membrane is one of the critical parameters for understanding and predicting membrane protein stability, and understanding membrane protein function. Transmembrane segments are generally very hydrophobic, but may contain hydrophilic residues that are important for the structure or function of the protein. Experimental and theoretical studies have shown that the presence of polar residues, such as Asn, can lead to the formation of helical aggregates (Stockner et al., 2004; Tatko et al., 2006). The crystal structures of the voltage-gated potassium channels KvAP (Jiang et al., 2003a) and Kv1.2 (Long et al., 2005) have caused vigorous debate in the ion channel community as some models proposed based on the crystal structures would have the arginine gating charges exposed to the lipid environment (Jiang et al., 2003b). After the publication of the KvAP crystal structure, it was argued that it was next to impossible to put an arginine in a lipid-exposed environment, and that the activation energy for such a model would be far too high to be realistic (Grabe et al., 2004). However, a recent experimental study has shown that the S4 segment of KvAP, which contains the gating charges, is able to insert into the membrane as a marginally stable transmembrane helix (Hessa et al., 2005b).