The Inhibitory γ Subunit of the Rod cGMP Phosphodiesterase Binds the Catalytic Subunits in an Extended Linear Structure

Lian-Wang Guo; Hakim Muradov; Abdol R Hajipour; Michael K Sievert; Nikolai O Artemyev; Arnold E Ruoho

doi:10.1074/jbc.M600595200

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The Inhibitory γ Subunit of the Rod cGMP Phosphodiesterase Binds the Catalytic Subunits in an Extended Linear Structure

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The Inhibitory γ Subunit of the Rod cGMP Phosphodiesterase Binds the Catalytic Subunits in an Extended Linear Structure

Lian-Wang Guo, Hakim Muradov, Abdol R Hajipour, Michael K Sievert, Nikolai O Artemyev and Arnold E Ruoho

The Journal of biological chemistry, Vol.281(22), pp.15412-15422

06/02/2006

DOI: 10.1074/jbc.M600595200

PMID: 16595671

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Abstract

The unique feature of rod photoreceptor cGMP phosphodiesterase (PDE6) is the presence of inhibitory subunits (Pγ), which interact with the catalytic heterodimer (Pαβ) to regulate its activity. This uniqueness results in an extremely high sensitivity and sophisticated modulations of rod visual signaling where the Pγ/Pαβ interactions play a critical role. The quaternary organization of the αβγγ heterotetramer is poorly understood and contradictory patterns of interaction have been previously suggested. Here we provide evidence that supports a specific interaction, by systematically and differentially analyzing the Pγ-binding regions on Pα and Pβ through photolabel transfer from various Pγ positions throughout the entire molecule. The Pγ N-terminal Val16–Phe30 region was found to interact with the Pαβ GAFa domain, whereas its C terminus (Phe73–Ile87) interacted with the Pαβ catalytic domain. The interactions of Pγ with these two domains were bridged by its central Ser40–Phe50 region through interactions with GAFb and the linker between GAFb and the catalytic domain, indicating a linear and extended interaction between Pγ and Pαβ. Furthermore, a photocross-linked product αβγ(γ) was specifically generated by the double derivatized Pγ, in which one photoprobe was located in the polycationic region and the other in the C terminus. Taken together the evidence supports the conclusion that each Pγ molecule binds Pαβ in an extended linear interaction and may even interact with both Pα and Pβ simultaneously.

Details

Title: Subtitle: The Inhibitory γ Subunit of the Rod cGMP Phosphodiesterase Binds the Catalytic Subunits in an Extended Linear Structure
Creators: Lian-Wang Guo - Department of Pharmacology, University of Wisconsin Medical School, Madison, Wisconsin 53706
Hakim Muradov - Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242
Abdol R Hajipour - Department of Pharmacology, University of Wisconsin Medical School, Madison, Wisconsin 53706
Michael K Sievert - Department of Pharmacology, University of Wisconsin Medical School, Madison, Wisconsin 53706
Nikolai O Artemyev - Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242
Arnold E Ruoho - Department of Pharmacology, University of Wisconsin Medical School, Madison, Wisconsin 53706
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.281(22), pp.15412-15422
DOI: 10.1074/jbc.M600595200
PMID: 16595671
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Language: English
Date published: 06/02/2006
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9984070987302771

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