PMC:2724026 / 29875-31398 JSONTXT

{"project":"2_test","denotations":[{"id":"19362094-19075236-62520550","span":{"begin":1240,"end":1242},"obj":"19075236"}],"text":"Our Φ-value analysis of the complex all-alpha Greek key FADD DD reveals a striking resemblance to the all-beta Greek key Ig-like domains. Both fold via diffuse transition states and, importantly, long-range interactions between the four central elements of structure are established in the TS. This ensures the topology is established with the correct orientation and pairing of the helices/strands and correct packing of the helix/strand pairs that make up the central hydrophobic core of both proteins. The elements of secondary structure that are less tightly associated with the central core are less well packed in the TS in both cases. Topology appears to be the dominant factor in determining the pathway of folding in all Greek key domains studied to date. However, secondary structure also has a role: whereas in the all-beta Ig-like domains, long-range, tertiary interactions dominate the folding process, in the DD studied here, short-range, local interactions are also important in the folding process, reflecting the helical secondary structure. A recent theoretical study suggests that topology is likely to be the dominant factor in determining folding pathways in all-beta proteins where long-range interactions predominate.12 However, in all-alpha proteins, where the majority of stabilising interactions are local, sequence changes are more likely to result in variable folding pathways within a family. The Greek key DDs appear to be an ideal family for the investigation of this theoretical observation."}