Betaalpha-hairpin clamps brace betaalphabeta modules and can make substantive contributions to the stability of TIM barrel proteins.
Non-local hydrogen bonding interactions between main chain amide hydrogen atoms and polar side chain acceptors that bracket consecutive betaalpha or alphabeta elements of secondary structure in alphaTS from E. coli, a TIM barrel protein, have previously been found to contribute 4-6 kcal mol(-1) to the stability of the native conformation. Experimental analysis of similar betaalpha-hairpin clamps in a homologous pair of TIM barrel proteins of low sequence identity, IGPS from S. solfataricus and E. coli, reveals that this dramatic enhancement of stability is not unique to alphaTS. A survey of 71 TIM barrel proteins demonstrates a 4-fold symmetry for the placement of betaalpha-hairpin clamps, bracing the fundamental betaalphabeta building block and defining its register in the (betaalpha)(8) motif. The preferred sequences and locations of betaalpha-hairpin clamps will enhance structure prediction algorithms and provide a strategy for engineering stability in TIM barrel proteins.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Xiaoyan
X
Yang
Sagar V
SV
Kathuria
Ramakrishna
R
Vadrevu
C Robert
CR
Matthews
D000465:Algorithms; D001426:Bacterial Proteins / Q000737:chemistry*; D002942:Circular Dichroism; D004926:Escherichia coli / Q000378:metabolism; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008968:Molecular Conformation; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016944:Sulfolobus / Q000378:metabolism; D013816:Thermodynamics
D001426:Bacterial Proteins