Diabetes mutations delineate an atypical POU domain in HNF-1alpha.
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Chi YI, Frantz JD, Oh BC, Hansen L, Dhe-Paganon S, Shoelson SE
Diabetes mutations delineate an atypical POU domain in HNF-1alpha.
Mol Cell. 2002 Nov;10(5):1129-37.
- PubMed ID
- 12453420 [ View in 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.