8T71

Crystal Structure of WT KRAS4a with bound GDP and Mg ion

8T71 の概要

• エントリーDOI: 10.2210/pdb8t71/pdb
• 分子名称: GTPase KRas, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: ras, kras, oncoprotein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41819.26

構造登録者

Tran, T.H.,Whitley, M.J.,Dharmaiah, S.,Simanshu, D.K. (登録日: 2023-06-19, 公開日: 2024-02-14, 最終更新日: 2024-10-30)

主引用文献

Whitley, M.J.,Tran, T.H.,Rigby, M.,Yi, M.,Dharmaiah, S.,Waybright, T.J.,Ramakrishnan, N.,Perkins, S.,Taylor, T.,Messing, S.,Esposito, D.,Nissley, D.V.,McCormick, F.,Stephen, A.G.,Turbyville, T.,Cornilescu, G.,Simanshu, D.K.
Comparative analysis of KRAS4a and KRAS4b splice variants reveals distinctive structural and functional properties.
Sci Adv, 10:eadj4137-eadj4137, 2024

PubMed Abstract: , the most frequently mutated oncogene in human cancer, produces two isoforms, KRAS4a and KRAS4b, through alternative splicing. These isoforms differ in exon 4, which encodes the final 15 residues of the G-domain and hypervariable regions (HVRs), vital for trafficking and membrane localization. While KRAS4b has been extensively studied, KRAS4a has been largely overlooked. Our multidisciplinary study compared the structural and functional characteristics of KRAS4a and KRAS4b, revealing distinct structural properties and thermal stability. Position 151 influences KRAS4a's thermal stability, while position 153 affects binding to RAF1 CRD protein. Nuclear magnetic resonance analysis identified localized structural differences near sequence variations and provided a solution-state conformational ensemble. Notably, exhibits substantial transcript abundance in bile ducts, liver, and stomach, with transcript levels approaching in the colon and rectum. Functional disparities were observed in full-length KRAS variants, highlighting the impact of HVR variations on interaction with trafficking proteins and downstream effectors like RAF and PI3K within cells.

PubMed: 38354232
DOI: 10.1126/sciadv.adj4137

実験手法

X-RAY DIFFRACTION (1.8 Å)