Structure of bhpBR3, the BAFF-binding loop of BR3 embedded in a beta-hairpin peptide
BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2.
THE RECEPTOR LOOP IS EMBEDDED WITHIN A BETA-HAIRPIN (BHP) SCAFFOLD
Tumor necrosis factor receptor superfamily member 13C, B cell-activating factor receptor, BAFF receptor, BAFF-R, BLys receptor 3
SEQUENCE THIS IS PART OF AN OPTIMIZED BETA-HAIRPIN SCAFFOLD, (SEE RUSSELL, BLANDL, SKELTON, & COCHRAN, "STABILITY OF CYCLIC BETA-HAIRPINS: ASYMMETRIC CONTRIBUTIONS FROM SIDE CHAINS OF A HYDROGEN-BONDED CROSS-STRAND RESIDUE PAIR", J. AMER. CHEM. SOC., IN PRESS.)
The Peptide was synthesized chemically with acetylated N-terminus and amidated C-terminus
structures with the least restraint violations
Complete 1H resonance assignments were obtained using standard 2D homonuclear NMR methods. Distance restraints were derived from analysis of a 2D NOESY spectrum (250ms mixing time); HN-Ha coupling constants were obtained from analysis of a DQF-COSY spectrum acquired in water; and HaHb values were obtained from analysis of a COSY-35 spectrum acquired in D2O. Structures were calculated from a total of 119 NOE-derived (including 46 long-range) distance restraints and 16 dihedral angle restraints. Structures satisfy the experimental data very well with no distance or dihedral angle violations greater than 0.1 angstrom or 1 degree, respectively.
hybrid distance geometry/simulated annealing followed by restrained molecular dynamics.