6Y31

NG domain of human SRP54 T117 deletion mutant

6Y31 の概要

• エントリーDOI: 10.2210/pdb6y31/pdb
• 分子名称: Signal recognition particle 54 kDa protein (1 entity in total)
• 機能のキーワード: srp54 ng domain, protein translocation, severe congenital neutropenia, disease mutant, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 133642.42

構造登録者

Juaire, K.D.,Lapouge, K.,Becker, M.M.M.,Kotova, I.,Haas, M.,Carapito, R.,Wild, K.,Bahram, S.,Sinning, I. (登録日: 2020-02-17, 公開日: 2020-09-23, 最終更新日: 2024-01-24)

主引用文献

Juaire, K.D.,Lapouge, K.,Becker, M.M.M.,Kotova, I.,Michelhans, M.,Carapito, R.,Wild, K.,Bahram, S.,Sinning, I.
Structural and Functional Impact of SRP54 Mutations Causing Severe Congenital Neutropenia.
Structure, 29:15-, 2021

PubMed Abstract: The SRP54 GTPase is a key component of co-translational protein targeting by the signal recognition particle (SRP). Point mutations in SRP54 have been recently shown to lead to a form of severe congenital neutropenia displaying symptoms overlapping with those of Shwachman-Diamond syndrome. The phenotype includes severe neutropenia, exocrine pancreatic deficiency, and neurodevelopmental as well as skeletal disorders. Using a combination of X-ray crystallography, hydrogen-deuterium exchange coupled to mass spectrometry and complementary biochemical and biophysical methods, we reveal extensive structural defects in three disease-causing SRP54 variants resulting in critical protein destabilization. GTP binding is mostly abolished as a consequence of an altered GTPase core. The mutations located in conserved sequence fingerprints of SRP54 eliminate targeting complex formation with the SRP receptor as demonstrated in yeast and human cells. These specific defects critically influence the entire SRP pathway, thereby causing this life-threatening disease.

PubMed: 33053321
DOI: 10.1016/j.str.2020.09.008

実験手法

X-RAY DIFFRACTION (4.001 Å)