Download MendeleyDiabetes mutations delineate an atypical POU domains in HNF1-Alpha
Chi, Y.-I., Frantz, J.D., Oh, B.-C., Hansen, L., Dhe-Paganon, S., Shoelson, S.E.(2002) Mol Cell 10: 1129-1137
- PubMed: 12453420
- DOI: https://doi.org/10.1016/s1097-2765(02)00704-9
- Primary Citation of Related Structures:
1IC8 - PubMed Abstract:
Mutations in Hnf-1alpha are the most common Mendelian cause of diabetes mellitus. To elucidate the molecular function of a mutational hotspot, we cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules are bound to the promoter. Each contains a homeodomain and a second domain structurally similar to POU-specific domains that was not predicted on the basis of amino acid sequence. Atypical elements in both domains create a stable interface that further distinguishes HNF-1alpha from other flexible POU-homeodomain proteins. The numerous diabetes-causing mutations in HNF-1alpha thus identified a previously unrecognized POU domain which was used as a search model to identify additional POU domain proteins in sequence databases.
Organizational Affiliation:
Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
