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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Chi YI,Frantz JD,Oh BC,Hansen L,Dhe-Paganon S,Shoelson SEdoi
10.1016/s1097-2765(02)00704-9subject
Has Abstractpub_date
2002-11-01 00:00:00pages
1129-37issue
5eissn
1097-2765issn
1097-4164pii
S1097-2765(02)00704-9journal_volume
10pub_type
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