The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged helix domain
type: Dataset
contact point: Organization
  fn: CCSD
keyword: journal-articles
keyword: infoeu-reposemanticsarticle
keyword: transcription
keyword: man1
keyword: dna
keyword: r-smad
keyword: regulation
keyword: winged-helix-motif
keyword: sdvbbmlife-sciences-q-biobiochemistry-molecular-biology
landing page: 0021-9258
description: is an integral protein of the inner nuclear membrane, which interacts with nuclear lamins and emerin, thus playing a role in nuclear organization. It also binds to chromatin-associated proteins and transcriptional regulators, including the R-Smads, Smad1, Smad2 and Smad3. Mutations in the human gene encoding MAN1 cause sclerosing bone dysplasias, which sometimes have associated skin abnormalities. At the molecular level, these mutations lead to loss of the MAN1 / R-Smads interaction, thus perturbing transforming growth factor superfamily signaling pathway. As a first step to understand the physical basis of MAN1 interaction with R-Smads, we here report the structural characterization of the carboxyl-terminal nucleoplasmic region of MAN1, which is responsible for Smad binding. This region exhibits an amino-terminal globular domain adopting a winged helix fold, as found in several Smad-associated sequence-specific DNA binding factors. Consistently, it binds to DNA through the positively charged recognition helix H3 of its winged helix motif. However, it does not show the predicted carboxyl-terminal U2AF homology domain in solution, suggesting that the folding and stability of such a domain in MAN1 depend upon binding to an unidentified partner. Modeling the complex between DNA and the winged helix domain shows that the regions involved in DNA binding are essentially distinct from those reported to be involved in Smad binding. This suggests that MAN1 binds simultaneously to R-Smads and their targeted DNA sequences.
issued: 2026-05-27T22:43:09.809358
language: en
modified: 2026-05-27T22:43:09.809368

test_moissonnage_selune
type: Agent

The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged helix domain
type: Distribution
access URL: https://hal.science/hal-00023616
format: HTML
issued: 2026-05-27T22:43:09.958798
modified: 2026-05-27T22:43:09.711559