Structural Basis for Induced Fit Mechanisms in DNA Recognition by the Pdx1 Homeodomain

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• 作者：Antonella Longo ; Gerald P. Guanga ; Robert B. Rose
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：March 20, 2007
• 年：2007
• 卷：46
• 期：11
• 页码：2948 - 2957
• 全文大小：952K
• 年卷期：v.46,no.11(March 20, 2007)
• ISSN：1520-4995

文摘

Pancreatic and duodenal homeobox 1 (Pdx1) is a homeodomain transcription factor belongingto the ParaHox family. Pdx1 plays an essential role in pancreatic endocrine and exocrine cell developmentand maintenance of adult islet mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-cell function. Mutations in the human pdx1 gene are linked to an earlyonset form of non-insulin-dependent diabetes mellitus, MODY-4. We demonstrate that the homeodomainreproduces the binding specificity of the full-length protein. We report the 2.4 Å resolution crystal structureof the homeodomain bound to a target DNA. The two Pdx1/DNA complexes in the asymmetric unitdisplay conformational differences: in the DNA curvature, the orientation of the homeodomain in themajor groove, and the order of the N-terminal arm. Comparing the two complexes indicates invariantprotein-DNA contacts, and variant contacts that are unique to each binding orientation. An induced fitmodel is proposed that depends on the DNA conformation and provides a mechanism for nonlocalcontributions to binding specificity.