PMC:2724026 / 27587-29862 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2724026","sourcedb":"PMC","sourceid":"2724026","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2724026","text":"Comparison with other helix bundles\nA number of helix-bundle proteins have been studied. FADD DD differs from all of these helical proteins in terms of structure, as three distinct hydrophobic cores can be identified. Here we compare the folding of FADD DD with simple helix bundle proteins. We largely ignore the cytochrome c proteins where the haem provides essential stability to the protein,46 and the much larger globins, which have more complex hierarchical folding mechanisms.47–50\nFormation of the central core of FADD involves packing of a four-helix bundle. Several other four-helix bundle proteins have been studied in detail by Φ-value analysis; two members of the ACBP family51 and apocytochrome b56252 (which are up-down helical bundles) and Im7, the homologous Im98 and the FF domain of HYPA/FBP1153 (which have three long helices plus a shorter helix). In all these cases, formation of the TS involves packing of three helices with one helix being essentially unstructured. It has been suggested that the early, obligatory stages in nucleation of folding will be formation of the interactions that are necessary to establish the overall topology.54–56 Packing of three helices in a simple four-helix bundle is sufficient to establish the topology. It seems probable that the more complex Greek key topology of the DD requires all four central elements to be assembled, as was found in the Ig-like Greek key domains.\nThe folding of the two three-helix bundles of FADD DD can be compared with the folding of other three-helix bundle proteins. A number of these have been studied extensively, using Φ-value analysis. In some cases, one well-formed helix is observed in the TS with other elements of structure packed against it (as, for example, in protein A27,57), whereas in others, two elements of structure come together with the third helix relatively unstructured (e.g. spectrin domains17,18 and peripheral subunit binding domains58). The three-helix bundles of FADD DD fall into this second category. Interestingly, as in the spectrin domains, the helices that are in contact are those that are separated in sequence (H1 with H5 and H2 with H4). This suggests that formation of these long-range interactions is the important step for folding these bundles.","divisions":[{"label":"title","span":{"begin":0,"end":35}},{"label":"p","span":{"begin":36,"end":488}},{"label":"p","span":{"begin":489,"end":1431}}],"tracks":[{"project":"2_test","denotations":[{"id":"19362094-15663948-62520540","span":{"begin":395,"end":397},"obj":"15663948"},{"id":"19362094-18187151-62520541","span":{"begin":486,"end":488},"obj":"18187151"},{"id":"19362094-16300787-62520541","span":{"begin":486,"end":488},"obj":"16300787"},{"id":"19362094-18384808-62520541","span":{"begin":486,"end":488},"obj":"18384808"},{"id":"19362094-18779573-62520541","span":{"begin":486,"end":488},"obj":"18779573"},{"id":"19362094-15690348-62520542","span":{"begin":688,"end":690},"obj":"15690348"},{"id":"19362094-15533036-62520543","span":{"begin":710,"end":715},"obj":"15533036"},{"id":"19362094-12547210-62520544","span":{"begin":778,"end":780},"obj":"12547210"},{"id":"19362094-15935381-62520545","span":{"begin":810,"end":814},"obj":"15935381"},{"id":"19362094-16678203-62520546","span":{"begin":1165,"end":1167},"obj":"16678203"},{"id":"19362094-11214326-62520546","span":{"begin":1165,"end":1167},"obj":"11214326"},{"id":"19362094-16782128-62520547","span":{"begin":1773,"end":1775},"obj":"16782128"},{"id":"19362094-18625237-62520547","span":{"begin":1773,"end":1775},"obj":"18625237"},{"id":"19362094-15504412-62520548","span":{"begin":1907,"end":1909},"obj":"15504412"},{"id":"19362094-16618492-62520548","span":{"begin":1907,"end":1909},"obj":"16618492"},{"id":"19362094-18625240-62520549","span":{"begin":1948,"end":1950},"obj":"18625240"}],"attributes":[{"subj":"19362094-15663948-62520540","pred":"source","obj":"2_test"},{"subj":"19362094-18187151-62520541","pred":"source","obj":"2_test"},{"subj":"19362094-16300787-62520541","pred":"source","obj":"2_test"},{"subj":"19362094-18384808-62520541","pred":"source","obj":"2_test"},{"subj":"19362094-18779573-62520541","pred":"source","obj":"2_test"},{"subj":"19362094-15690348-62520542","pred":"source","obj":"2_test"},{"subj":"19362094-15533036-62520543","pred":"source","obj":"2_test"},{"subj":"19362094-12547210-62520544","pred":"source","obj":"2_test"},{"subj":"19362094-15935381-62520545","pred":"source","obj":"2_test"},{"subj":"19362094-16678203-62520546","pred":"source","obj":"2_test"},{"subj":"19362094-11214326-62520546","pred":"source","obj":"2_test"},{"subj":"19362094-16782128-62520547","pred":"source","obj":"2_test"},{"subj":"19362094-18625237-62520547","pred":"source","obj":"2_test"},{"subj":"19362094-15504412-62520548","pred":"source","obj":"2_test"},{"subj":"19362094-16618492-62520548","pred":"source","obj":"2_test"},{"subj":"19362094-18625240-62520549","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec93bc","default":true}]}]}}