3DBA

Crystal structure of the cGMP-bound GAF a domain from the photoreceptor phosphodiesterase 6C

3DBA の概要

• エントリーDOI: 10.2210/pdb3dba/pdb
• 分子名称: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha', GUANOSINE-3',5'-MONOPHOSPHATE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: 3', 5' cgmp, gaf domain, cyclic nucleotide phosphodiesterase, cgmp, hydrolase, lipoprotein, membrane, prenylation, sensory transduction, vision
• 由来する生物種: Gallus gallus (bantam,chickens)
• 細胞内の位置: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P52731
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42602.76

構造登録者

Martinez, S.E.,Heikaus, C.C.,Klevit, R.E.,Beavo, J.A. (登録日: 2008-05-30, 公開日: 2008-07-01, 最終更新日: 2024-02-21)

主引用文献

Martinez, S.E.,Heikaus, C.C.,Klevit, R.E.,Beavo, J.A.
The Structure of the GAF A Domain from Phosphodiesterase 6C Reveals Determinants of cGMP Binding, a Conserved Binding Surface, and a Large cGMP-dependent Conformational Change.
J.Biol.Chem., 283:25913-25919, 2008

PubMed Abstract: The photoreceptor phosphodiesterase (PDE6) regulates the intracellular levels of the second messenger cGMP in the outer segments of cone and rod photoreceptor cells. PDE6 contains two regulatory GAF domains, of which one (GAF A) binds cGMP and regulates the activity of the PDE6 holoenzyme. To increase our understanding of this allosteric regulation mechanism, we present the 2.6A crystal structure of the cGMP-bound GAF A domain of chicken cone PDE6. Nucleotide specificity appears to be provided in part by the orientation of Asn-116, which makes two hydrogen bonds to the guanine ring of cGMP but is not strictly conserved among PDE6 isoforms. The isolated PDE6C GAF A domain is monomeric and does not contain sufficient structural determinants to form a homodimer as found in full-length PDE6C. A highly conserved surface patch on GAF A indicates a potential binding site for the inhibitory subunit Pgamma. NMR studies reveal that the apo-PDE6C GAF A domain is structured but adopts a significantly altered structural state indicating a large conformational change with rearrangement of secondary structure elements upon cGMP binding. The presented crystal structure will help to define the cGMP-dependent regulation mechanism of the PDE6 holoenzyme and its inhibition through Pgamma binding.

PubMed: 18614542
DOI: 10.1074/jbc.M802891200

実験手法

X-RAY DIFFRACTION (2.57 Å)