2GYT

Solution structure of the SAM (sterile alpha motif) domain of DLC1 (deleted in liver cancer 1)

2GYT の概要

• エントリーDOI: 10.2210/pdb2gyt/pdb
• NMR情報: BMRB: 7120
• 分子名称: Deleted in liver cancer 1 protein, isoform 2 (1 entity in total)
• 機能のキーワード: sam domain, protein structure, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (Potential): Q96QB1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8965.49

構造登録者

Yang, S. (登録日: 2006-05-10, 公開日: 2007-04-24, 最終更新日: 2024-05-29)

主引用文献

Zhong, D.,Zhang, J.,Yang, S.,Soh, U.J.K.,Buschdorf, J.P.,Zhou, Y.T.,Yang, D.,Low, B.C.
The SAM domain of the RhoGAP DLC1 binds EF1A1 to regulate cell migration
J.Cell.Sci., 122:414-424, 2009

PubMed Abstract: Deleted in liver cancer 1 (DLC1) is a multi-modular Rho-GTPase-activating protein (RhoGAP) and a tumor suppressor. Besides its RhoGAP domain, functions of other domains in DLC1 remain largely unknown. By protein precipitation and mass spectrometry, we identified eukaryotic elongation factor 1A1 (EF1A1) as a novel partner for the sterile alpha motif (SAM) domain of DLC1 but not the SAM domain of DLC2. The solution structure of DLC1 SAM revealed a new monomeric fold with four parallel helices, similar to that of DLC2 SAM but distinct from other SAM domains. Mutating F38, L39 and F40 within a hydrophobic patch retained its overall structure but abolished its interaction with EF1A1 with F38 and L39 forming an indispensable interacting motif. DLC1 SAM did not localize to and was not required for DLC1 to suppress the turnover of focal adhesions. Instead, DLC1 SAM facilitated EF1A1 distribution to the membrane periphery and ruffles upon growth factor stimulation. Compared with wild-type DLC1, the non-interactive DLC1 mutant is less potent in suppressing cell migration, whereas overexpression of the DLC1 SAM domain alone, but not the non-interactive mutant SAM or DLC2 SAM, greatly enhanced cell migration. This finding reveals a novel contribution of the SAM-EF1A1 interaction as a potentially important GAP-independent modulation of cell migration by DLC1.

PubMed: 19158340
DOI: 10.1242/jcs.027482

実験手法

SOLUTION NMR