4OKH

Crystal structure of calpain-3 penta-EF-hand domain

4OKH の概要

• エントリーDOI: 10.2210/pdb4okh/pdb
• 分子名称: Calpain-3, CALCIUM ION, 2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,62,65,68,71,74,77,80-HEPTACOSAOXADOOCTACONTAN-82-OL, ... (4 entities in total)
• 機能のキーワード: calcium-binding, ef-hand, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69529.20

構造登録者

Karunan Partha, S.,Ravulapalli, R.,Campbell, R.L.,Allingham, J.S.,Davies, P.L. (登録日: 2014-01-22, 公開日: 2014-05-28, 最終更新日: 2023-09-20)

主引用文献

Partha, S.K.,Ravulapalli, R.,Allingham, J.S.,Campbell, R.L.,Davies, P.L.
Crystal structure of calpain-3 penta-EF-hand (PEF) domain - a homodimerized PEF family member with calcium bound at the fifth EF-hand.
Febs J., 281:3138-3149, 2014

PubMed Abstract: Calpains are Ca(2+) dependent intracellular cysteine proteases that cleave a wide range of protein substrates to help implement Ca(2+) signaling in the cell. The major isoforms of this enzyme family, calpain-1 and calpain-2, are heterodimers of a large and a small subunit, with the main dimer interface being formed through their C-terminal penta-EF hand (PEF) domains. Calpain-3, or p94, is a skeletal muscle-specific isoform that is genetically linked to limb-girdle muscular dystrophy. Biophysical and modeling studies with the PEF domain of calpain-3 support the suggestion that full-length calpain-3 exists as a homodimer. Here, we report the crystallization of calpain-3's PEF domain and its crystal structure in the presence of Ca(2+) , which provides evidence for the homodimer architecture of calpain-3 and supports the molecular model that places a protease core at either end of the elongated dimer. Unlike other calpain PEF domain structures, the calpain-3 PEF domain contains a Ca(2+) bound at the EF5-hand used for homodimer association. Three of the four Ca(2+) -binding EF-hands of the PEF domains are concentrated near the protease core, and have the potential to radically change the local charge within the dimer during Ca(2+) signaling. Examination of the homodimer interface shows that there would be steric clashes if the calpain-3 large subunit were to try to pair with a calpain small subunit. Database Structural data are available in the Protein Data Bank database under accession number 4OKH.

PubMed: 24846670
DOI: 10.1111/febs.12849

実験手法

X-RAY DIFFRACTION (2.45 Å)