5FR3

X-ray crystal structure of aggregation-resistant protective antigen of Bacillus anthracis (mutant S559L T576E)

Summary for 5FR3

• Entry DOI: 10.2210/pdb5fr3/pdb
• Descriptor: PROTECTIVE ANTIGEN, CALCIUM ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: toxin, anthrax protective antigen
• Biological source: BACILLUS ANTHRACIS
• Cellular location: Secreted, extracellular space: P13423
• Total number of polymer chains: 1
• Total formula weight: 81515.57

Authors

Ganesan, A.,Siekierska, A.,Beerten, J.,Brams, M.,van Durme, J.,De Baets, G.,van der Kant, R.,Gallardo, R.,Ramakers, M.,Langenberg, T.,Wilkinson, H.,De Smet, F.,Ulens, C.,Rousseau, F.,Schymkowitz, J. (deposition date: 2015-12-15, release date: 2016-01-27, Last modification date: 2024-01-10)

Primary citation

Ganesan, A.,Siekierska, A.,Beerten, J.,Brams, M.,Van Durme, J.,De Baets, G.,Van Der Kant, R.,Gallardo, R.,Ramakers, M.,Langenberg, T.,Wilkinson, H.,De Smet, F.,Ulens, C.,Rousseau, F.,Schymkowitz, J.
Structural Hot Spots for the Solubility of Globular Proteins
Nat.Commun., 7:10816-, 2016

PubMed Abstract: Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher protein concentrations are often problematic. This raises the question whether the solubility of natural protein sequences can be improved. We here show an anti-correlation between the number of aggregation prone regions (APRs) in a protein sequence and its solubility, suggesting that mutational suppression of APRs provides a simple strategy to increase protein solubility. We show that mutations at specific positions within a protein structure can act as APR suppressors without affecting protein stability. These hot spots for protein solubility are both structure and sequence dependent but can be computationally predicted. We demonstrate this by reducing the aggregation of human α-galactosidase and protective antigen of Bacillus anthracis through mutation. Our results indicate that many proteins possess hot spots allowing to adapt protein solubility independently of structure and function.

PubMed: 26905391
DOI: 10.1038/NCOMMS10816

Experimental method

X-RAY DIFFRACTION (1.935 Å)