3P7Z

Crystal structure of the Neurofibromin Sec14-PH module containing the patient derived mutation I1584V

3P7Z の概要

• エントリーDOI: 10.2210/pdb3p7z/pdb
• 関連するPDBエントリー: 2e2x
• 分子名称: Neurofibromin, (1S)-2-{[(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: sec14 homolgy domain, pleckstrin homology domain, binding of glycerophospholipids, glycerophospholipids, cytoplasmatic, lipid binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65095.25

構造登録者

Welti, S.,Scheffzek, K. (登録日: 2010-10-13, 公開日: 2010-12-08, 最終更新日: 2024-11-06)

主引用文献

Welti, S.,Kuhn, S.,D'Angelo, I.,Brugger, B.,Kaufmann, D.,Scheffzek, K.
Structural and biochemical consequences of NF1 associated nontruncating mutations in the Sec14-PH module of neurofibromin.
Hum.Mutat., 32:191-197, 2011

PubMed Abstract: Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by alterations in the tumor suppressor gene NF1. Clinical manifestations include various neural crest derived tumors, pigmentation anomalies, bone deformations, and learning disabilities. NF1 encodes the Ras specific GTPase activating protein (RasGAP) neurofibromin, of which the central RasGAP related domain as well as a Sec14-like (residues 1560-1699) and a tightly interacting pleckstrin homology (PH)-like (1713-1818) domain are currently well defined. However, patient-derived nontruncating mutations have been reported along the whole NF1 gene, suggesting further essential protein functions. Focusing on the Sec14-PH module, we have engineered such nontruncating mutations and analyzed their implications on protein function and structure using lipid binding assays, CD spectroscopy and X-ray crystallography. Although lipid binding appears to be preserved among most nontruncating mutants, we see major structural changes for two of the alterations. Judging from these changes and our biochemical data, we suggest the presence of an intermolecular contact surface in the lid-lock region of the protein.

PubMed: 21089070
DOI: 10.1002/humu.21405

実験手法

X-RAY DIFFRACTION (2.65 Å)