1H, 13C and 15N assignments of EGF domains 8 to 11 of human Notch-1

The Notch receptor is part of a core cell-cell signaling system crucial for development and tissue homeostasis in Metazoa. Structural information is available for the negative regulatory region (NRR), the ligand-binding region and the intracellular domain (NICD) of Notch, but data for the remaining...

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Main Authors: Weisshuhn, P, Handford, P, Redfield, C
Format: Journal article
Published: Springer Netherlands 2015
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author Weisshuhn, P
Handford, P
Redfield, C
author_facet Weisshuhn, P
Handford, P
Redfield, C
author_sort Weisshuhn, P
collection OXFORD
description The Notch receptor is part of a core cell-cell signaling system crucial for development and tissue homeostasis in Metazoa. Structural information is available for the negative regulatory region (NRR), the ligand-binding region and the intracellular domain (NICD) of Notch, but data for the remaining portions of the extracellular region which determine its overall shape at the cell surface are still lacking. This region consists of 36 EGF-like domains arranged as multiple tandem repeats. Most EGF-like domains near the ligand binding domains EGF 11 and 12 are of the calcium-binding type, with well-described, rigid and near-linear interdomain interfaces. However, EGF10 is a conserved, non-calcium-binding domain which may confer flexibility or a non-linear organization to the receptor. To probe this, we have expressed and purified a four-domain construct, EGF8-11, from human Notch-1, and report here the <sup>1</sup>H, <sup>13</sup>C and <sup>15</sup>N resonance assignments. Differences in EGF11 chemical shifts between this construct and a previously assigned construct, EGF11-13, confirm the presence of hydrophobic interdomain contacts between the hairpin turn of the major andbeta;-sheet in EGF11 and the conserved aromatic residue within the C-terminal region of EGF10. This suggests that the EGF10-11 interface is rigid.
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spelling oxford-uuid:d5accbe2-6bc6-432e-b374-fdeef45eaccb2022-03-27T08:27:40Z1H, 13C and 15N assignments of EGF domains 8 to 11 of human Notch-1Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d5accbe2-6bc6-432e-b374-fdeef45eaccbSymplectic Elements at OxfordSpringer Netherlands2015Weisshuhn, PHandford, PRedfield, CThe Notch receptor is part of a core cell-cell signaling system crucial for development and tissue homeostasis in Metazoa. Structural information is available for the negative regulatory region (NRR), the ligand-binding region and the intracellular domain (NICD) of Notch, but data for the remaining portions of the extracellular region which determine its overall shape at the cell surface are still lacking. This region consists of 36 EGF-like domains arranged as multiple tandem repeats. Most EGF-like domains near the ligand binding domains EGF 11 and 12 are of the calcium-binding type, with well-described, rigid and near-linear interdomain interfaces. However, EGF10 is a conserved, non-calcium-binding domain which may confer flexibility or a non-linear organization to the receptor. To probe this, we have expressed and purified a four-domain construct, EGF8-11, from human Notch-1, and report here the <sup>1</sup>H, <sup>13</sup>C and <sup>15</sup>N resonance assignments. Differences in EGF11 chemical shifts between this construct and a previously assigned construct, EGF11-13, confirm the presence of hydrophobic interdomain contacts between the hairpin turn of the major andbeta;-sheet in EGF11 and the conserved aromatic residue within the C-terminal region of EGF10. This suggests that the EGF10-11 interface is rigid.
spellingShingle Weisshuhn, P
Handford, P
Redfield, C
1H, 13C and 15N assignments of EGF domains 8 to 11 of human Notch-1
title 1H, 13C and 15N assignments of EGF domains 8 to 11 of human Notch-1
title_full 1H, 13C and 15N assignments of EGF domains 8 to 11 of human Notch-1
title_fullStr 1H, 13C and 15N assignments of EGF domains 8 to 11 of human Notch-1
title_full_unstemmed 1H, 13C and 15N assignments of EGF domains 8 to 11 of human Notch-1
title_short 1H, 13C and 15N assignments of EGF domains 8 to 11 of human Notch-1
title_sort 1h 13c and 15n assignments of egf domains 8 to 11 of human notch 1
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