2HDL

Solution structure of Brak/CXCL14

2HDL の概要

• エントリーDOI: 10.2210/pdb2hdl/pdb
• NMR情報: BMRB: 7229
• 分子名称: Small inducible cytokine B14 (1 entity in total)
• 機能のキーワード: cxcl14, brak, chemokine, cytokine
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9500.20

構造登録者

Peterson, F.C.,Thorpe, J.A.,Harder, A.G.,Volkman, B.F.,Schwarze, S.R. (登録日: 2006-06-20, 公開日: 2006-10-24, 最終更新日: 2024-11-06)

主引用文献

Peterson, F.C.,Thorpe, J.A.,Harder, A.G.,Volkman, B.F.,Schwarze, S.R.
Structural Determinants Involved in the Regulation of CXCL14/BRAK Expression by the 26 S Proteasome.
J.Mol.Biol., 363:813-822, 2006

PubMed Abstract: The chemokine CXCL14/BRAK participates in immune surveillance by recruiting dendritic cells. CXCL14 gene expression is altered in a number of cancers, but protein expression levels have not been investigated. Here we report that CXCL14 protein can be expressed in primary epithelial cells; however, in several immortalized and cancer cell lines this protein is targeted for polyubiquitylation and proteasomal degradation. We determined the NMR structure of CXCL14 to identify motifs controlling its expression. CXCL14 adopts the canonical chemokine tertiary fold but contains a unique five amino acid insertion (41VSRYR45) relative to other CXC chemokines. Deletion or substitution of key residues within this insertion prevented proteasomal degradation. Furthermore, we defined a 15 amino acid fragment of CXCL14 that is sufficient to induce proteasomal degradation. This study elucidates a post-translational mechanism for the loss of CXCL14 in cancer and a novel mode of chemokine regulation.

PubMed: 16987528
DOI: 10.1016/j.jmb.2006.08.057

実験手法

SOLUTION NMR