Abstract
Halophilic proteins have greater abundance of acidic over basic and very low bulky hydrophobic residues. Classical electrostatic stabilization was suggested as the key determinant for halophilic adaptation of protein. However, contribution of specific electrostatic interactions (i.e. salt-bridges) to overall stability of halophilic proteins is yet to be understood. To understand this, we use Adaptive-Poison-Boltzmann-Solver Methods along with our home-built automation to workout net as well as associated component energy terms such as desolvation energy, bridge energy and background energy for 275 salt-bridges from 20 extremely halophilic proteins. We then perform extensive statistical analysis on general and energetic attributes on these salt-bridges. On average, 8 salt-bridges per 150 residues protein were observed which is almost twice than earlier report. Overall contributions of salt-bridges are −3.0 kcal mol−1. Majority (78%) of salt-bridges in our dataset are stable and conserved in nature. Although, average contributions of component energy terms are equal, their individual details vary greatly from one another indicating their sensitivity to local micro-environment. Notably, 35% of salt-bridges in our database are buried and stable. Greater desolvation penalty of these buried salt-bridges are counteracted by stable network salt-bridges apart from favorable equal contributions of bridge and background terms. Recruitment of extensive network salt-bridges (46%) with a net contribution of −5.0 kcal mol−1 per salt-bridge, seems to be a halophilic design wherein favorable average contribution of background term (−10 kcal mol−1) exceeds than that of bridge term (−7 kcal mol−1). Interiors of proteins from halophiles are seen to possess relatively higher abundance of charge and polar side chains than that of mesophiles which seems to be satisfied by cooperative network salt-bridges. Overall, our theoretical analyses provide insight into halophilic signature in its specific electrostatic interactions which we hope would help in protein engineering and bioinformatics studies.
Highlights
The family halobactereaceae or halophiles are archaea that thrive in natural habitat of saturated brine [1] and pH optima in neutral range
General characteristics of salt-bridges and its partners in halophilic proteins Halophilic proteins are reported to possess excess of negative charges over basic residues that contribute to the overall stability by non-specific electrostatic interactions [1,3,7,9,10,12,14,21]
Arguably specific electrostatic interactions which are less affected by the presence of multimolar salts [22] seem to have major contribution to the stability of halophilic proteins
Summary
The family halobactereaceae or halophiles are archaea that thrive in natural habitat of saturated brine [1] and pH optima in neutral range. The entire protein machinery of halophiles is dependent on high salt concentration for function and stability [2,3]. High concentration of salt is detrimental to mesophilic proteins. It enhances aggregation and collapse of 3D structure of proteins. It interferes with electrostatic interactions due to charge screening and reduces natural hydration of proteins [1]. In contrast to its mesophilic counterpart, halophilic proteins maintain structural and functional integrity only in saturated salt solution, withdrawal of which causes gradual loss of tertiary structure. At low salt condition such unfolding is caused both by non-specific electrostatic and hydrophobic destabilization [1,4,5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
