Intrinsically disordered γ-subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure

Jikui Song; Lian-Wang Guo; Hakim Muradov; Nikolai O Artemyev; Arnold E Ruoho; John L Markley

doi:10.1073/pnas.0709558105

Back

Intrinsically disordered γ-subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure

Journal article

Open access

Peer reviewed

Intrinsically disordered γ-subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure

Jikui Song, Lian-Wang Guo, Hakim Muradov, Nikolai O Artemyev, Arnold E Ruoho and John L Markley

Proceedings of the National Academy of Sciences - PNAS, Vol.105(5), pp.1505-1510

02/05/2008

DOI: 10.1073/pnas.0709558105

PMCID: PMC2234174

PMID: 18230733

Files and links (1)

url

https://doi.org/10.1073/pnas.0709558105View

Published (Version of record) Open Access

Abstract

The retinal phosphodiesterase (PDE6) inhibitory γ-subunit (PDEγ) plays a central role in vertebrate phototransduction through alternate interactions with the catalytic αβ-subunits of PDE6 and the α-subunit of transducin (αt). Detailed structural analysis of PDEγ has been hampered by its intrinsic disorder. We present here the NMR solution structure of PDEγ, which reveals a loose fold with transient structural features resembling those seen previously in the x-ray structure of PDEγ46–87 when bound to αt in the transition-state complex. NMR mapping of the interaction between PDEγ46–87 and the chimeric PDE5/6 catalytic domain confirmed that C-terminal residues 74–87 of PDEγ are involved in the association and demonstrated that its W70 indole group, which is critical for subsequent binding to αt, is left free at this stage. These results indicate that the interaction between PDEγ and αt during the phototransduction cascade involves the selection of preconfigured transient conformations.

Biological Sciences

protein recognition

visual transduction

NMR spectroscopy

transient structure

Details

Title: Subtitle: Intrinsically disordered γ-subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure
Creators: Jikui Song - Center for Eukaryotic Structural Genomics, Department of Biochemistry, University of Wisconsin, Madison, WI 53706-1544
Lian-Wang Guo - Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706-1544; and
Hakim Muradov - Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242
Nikolai O Artemyev - Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242
Arnold E Ruoho - Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706-1544; and
John L Markley - Center for Eukaryotic Structural Genomics, Department of Biochemistry, University of Wisconsin, Madison, WI 53706-1544
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.105(5), pp.1505-1510
DOI: 10.1073/pnas.0709558105
PMID: 18230733
PMCID: PMC2234174
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 02/05/2008
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9984025306402771

Metrics

12 Record Views

82 Times Cited - Web of Science