4HHV

Crystal structure of ceramide transfer protein pleckstrin homology domain

4HHV の概要

• エントリーDOI: 10.2210/pdb4hhv/pdb
• 分子名称: Collagen type IV alpha-3-binding protein, SULFATE ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: pleckstrin homology domain fold, binds to phosphatidylinositol 4-phosphate, lipid transport
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9Y5P4
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25210.81

構造登録者

Prashek, J.,Truong, T.,Yao, X. (登録日: 2012-10-10, 公開日: 2013-11-27, 最終更新日: 2024-02-28)

主引用文献

Prashek, J.,Truong, T.,Yao, X.
Crystal Structure of the Pleckstrin Homology Domain from the Ceramide Transfer Protein: Implications for Conformational Change upon Ligand Binding.
Plos One, 8:e79590-e79590, 2013

PubMed Abstract: Ceramide transfer protein (CERT) is responsible for the nonvesicular trafficking of ceramide from the endoplasmic reticulum (ER) to the trans Golgi network where it is converted to sphingomyelin (SM). The N-terminal pleckstrin homology (PH) domain is required for Golgi targeting of CERT by recognizing the phosphatidylinositol 4-phosphate (PtdIns(4)P) enriched in the Golgi membrane. We report a crystal structure of the CERT PH domain. This structure contains a sulfate that is hydrogen bonded with residues in the canonical ligand-binding pocket of PH domains. Our nuclear magnetic resonance (NMR) chemical shift perturbation (CSP) analyses show sulfate association with CERT PH protein resembles that of PtdIns(4)P, suggesting that the sulfate bound structure likely mimics the holo form of CERT PH protein. Comparison of the sulfate bound structure with the apo form solution structure shows structural rearrangements likely occur upon ligand binding, suggesting conformational flexibility in the ligand-binding pocket. This structural flexibility likely explains CERT PH domain's low affinity for PtdIns(4)P, a property that is distinct from many other PH domains that bind to their phosphoinositide ligands tightly. This unique structural feature of CERT PH domain is probably tailored towards the transfer activity of CERT protein where it needs to shuttle between ER and Golgi and therefore requires short resident time on ER and Golgi membranes.

PubMed: 24260258
DOI: 10.1371/journal.pone.0079590

実験手法

X-RAY DIFFRACTION (1.75 Å)