Elucidation of the ATP7B N-Domain Mg2+-ATP Coordination Site and Its Allosteric Regulation

Claude Hercend; Cyril Bauvais; Guillaume Bollot; Nicolas Delacotte; Philippe Chappuis; France Woimant; Jean-Marie Launay; Philippe Manivet

Elucidation of the ATP7B N-Domain Mg2+-ATP Coordination Site and Its Allosteric Regulation

Claude Hercend ^{1, 2} Cyril Bauvais ³ Guillaume Bollot ³ Nicolas Delacotte ³ Philippe Chappuis ¹ France Woimant ¹ Jean-Marie Launay ^{1, 2} Philippe Manivet ^{1, 4}

1 Hôpital Lariboisière

2 BioCANVAS - Biomarqueurs CArdioNeuroVASCulaires

3 Synsight

4 SABNP - Structure et activité des biomolécules normales et pathologiques

Abstract : The diagnostic of orphan genetic disease is often a puzzling task as less attention is paid to the elucidation of the pathophysiology of these rare disorders at the molecular level. We present here a multidisciplinary approach using molecular modeling tools and surface plasmonic resonance to study the function of the ATP7B protein, which is impaired in the Wilson disease. Experimentally validated in silico models allow the elucidation in the Nucleotide binding domain (N-domain) of the Mg 2+-ATP coordination site and answer to the controversial role of the Mg 2+ ion in the nucleotide binding process. The analysis of protein motions revealed a substantial effect on a long flexible loop branched to the N-domain protein core. We demonstrated the capacity of the loop to disrupt the interaction between Mg 2+-ATP complex and the N-domain and propose a role for this loop in the allosteric regulation of the nucleotide binding process.

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Complete list of metadatas

Cited literature [55 references] Display Hide Download

https://hal-univ-evry.archives-ouvertes.fr/hal-02321495
Contributor : Olek Maciejak <>
Submitted on : Monday, October 21, 2019 - 11:52:54 AM
Last modification on : Saturday, November 9, 2019 - 8:48:02 PM

(2011) Elucidation of the ATP7...

Publication funded by an institution

Elucidation of the ATP7B N-Domain Mg2+-ATP Coordination Site and Its Allosteric Regulation

File

Identifiers

Collections

Citation

Export

Metrics

20

38

Elucidation of the ATP7B N-Domain Mg2+-ATP Coordination Site and Its Allosteric Regulation

File

Identifiers

Collections

Citation

Export

Share

Metrics

20

38