Cryo-EM density map fitting driven in-silico structure of human soluble guanylate cyclase (hsGC) reveals functional aspects of inter-domain cross talk upon NO binding
Cryo-EM density map fitting driven in-silico structure of human soluble guanylate cyclase (hsGC) reveals functional aspects of inter-domain cross talk upon NO binding
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Tarih
2019-01-01
Yazarlar
Khalid, Rana Rehan
Maryam, Arooma
Fadouloglou, Vasiliki E.
Siddiqi, Abdul Rauf
Zhang, Yang
Süreli Yayın başlığı
Süreli Yayın ISSN
Cilt Başlığı
Yayınevi
ELSEVIER SCIENCE INC
Dergi Adı
JOURNAL OF MOLECULAR GRAPHICS \& MODELLING
Özet
The human soluble Guanylate Cyclase (hsGC) is a heterodimeric heme-containing enzyme which regulates many important physiological processes. In eukaryotes, hsGC is the only known receptor for nitric oxide (NO) signaling. Improper NO signaling results in various disease conditions such as neuro-degeneration, hypertension, stroke and erectile dysfunction. To understand the mechanisms of these diseases, structure determination of the hsGC dimer complex is crucial. However, so far all the attempts for the experimental structure determination of the protein were unsuccessful. The current study explores the possibility to model the quaternary structure of hsGC using a hybrid approach that combines state-of-the-art protein structure prediction tools with cryo-EM experimental data. The resultant 3D model shows close consistency with structural and functional insights extracted from biochemistry experiment data. Overall, the atomic-level complex structure determination of hsGC helps to unveil the inter-domain communication upon NO binding, which should be of important usefulness for elucidating the biological function of this important enzyme and for developing new treatments against the hsGC associated human diseases. (C) 2019 Elsevier Inc. All rights reserved.
Açıklama
Anahtar kelimeler
Homology modelling, Single/multiple-chain threading, Protein-protein docking, Multi-domain assembly, Cryo-EM density map fitting