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Characterization of the second ion-binding site in the G domain of H-Ras.
MedLine Citation:
PMID:  23148511     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Ras is a small monomeric GTPase acting as molecular switch in multiple cellular processes. The N-terminal G domain of Ras binds GTP or GDP accompanied by a magnesium ion, which is strictly required for GTPase activity and performs a structural role. Another ion-binding site on the opposite face of the G domain has been recently observed to specifically associate with calcium acetate in the crystal [Burhman et al, (2010) PNAS 107, 4931-4936]. In this article, we report thermodynamic measurements of affinity and specificity of the remote ion-binding site in H-Ras as observed in solution. Using 15N-1H NMR spectroscopy we determined that, in contrast to the crystalline state, the remote site in solution is specific for a divalent cation-binding both calcium and magnesium with anions playing a minimal role. The affinity of the remote site for divalent cations is in the low millimolar range and remarkably different for GDP- and GppNHp-bound forms of the G domain indicating that the GTP-binding pocket and the remote site are allosterically coupled through the distance of more than 25 Å. Considering that the remote site is oriented towards the membrane surface in vivo, we hypothesize that its cognate biological ligand might be a positively charged group extending from a lipid or an integral membrane protein.
Authors:
Casey O'Connor; Evgenii L Kovrigin
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-13
Journal Detail:
Title:  Biochemistry     Volume:  -     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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