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Unique RING finger structure from the human HRD1 protein
Author(s) -
Miyamoto Kazuhide,
Taguchi Yukari,
Saito Kazuki
Publication year - 2019
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.3532
Subject(s) - ring (chemistry) , ring finger , endoplasmic reticulum , zinc finger , chemistry , crystallography , biochemistry , organic chemistry , transcription factor , gene
Artificial RING fingers (ARFs) are created by transplanting active sites of RING fingers onto cross‐brace structures. Human hydroxymethylglutaryl‐coenzyme A reductase degradation protein 1 (HRD1) is involved in the degradation of the endoplasmic reticulum (ER) proteins. HRD1 possesses the RING finger domain (HRD1_RING) that functions as a ubiquitin‐ligating (E3) enzyme. Herein, we determined the solution structure of HRD1_RING using nuclear magnetic resonance (NMR). Moreover, using a metallochromic indicator, we determined the stoichiometry of zinc ions spectrophotometrically and found that HRD1_RING binds to two zinc atoms. The Simple Modular Architecture Research Tool database predicted the structure of HRD1_RING as a typical RING finger. However, it was found that the actual structure of HRD1_RING adopts an atypical RING‐H 2 type RING fold. This structural analysis unveiled the position and range of the active site of HRD1_RING that contribute to its specific ubiquitin‐conjugating enzyme (E2)‐binding capability.