A Comparison between Transmembrane Helices and Reentrant Loops

Reentrant loops are an important structure motif in a-helical transmembrane proteins. A reentrant loop goes half way through the membrane and turns and exits the membrane in the same side it has entered. To better predict the topology of transmembrane proteins and understand their function, it is important to investigate why the reentrant loops form such a unique topology. Herein, we compare the reentrant loops with transmembrane helices and find that the two types of structure motifs differ significantly in residue composition and the difference in reside composition is sufficient to discriminate reentrant loops from transmembrane helices based on the amino acid sequence. Our study shows that the difference in residue composition makes the reentrant loops less hydrophobic than the transmembrane helices. Because of the hydrophobic environment of the lipid membrane, this reduced hydrphobicity in the reentrant loops will make them less stable inside the membrane. That may be one of the many factors that make the reentrant loops to form such a unique topology.