TY - JOUR
T1 - Determination of the Secondary Structure and Folding Topology of Human Interleukin-4 Using Three-Dimensional Heteronuclear Magnetic Resonance Spectroscopy
AU - Powers, Robert
AU - Garrett, Daniel S.
AU - March, Carl J.
AU - Frieden, Eric A.
AU - Gronenbom, Angela M.
AU - Clore, G. Marius
PY - 1992
Y1 - 1992
N2 - The secondary structure of human recombinant interleukin-4 (IL-4) has been investigated by three-dimensional (3D) 15N- and 13C-edited nuclear Overhauser (NOE) spectroscopy on the basis of the 1H, 15N, and 13C assignments presented in the preceding paper [Powers, R., Garrett, D. S., March, C. J., Frieden, E. A., Gronenborn, A. M., ' Clore, G. M., (1992) Biochemistry (preceding paper in this issue)]. Based on the NOE data involving the NH, CαH, and CβH protons, as well as 3JHnα coupling constant, amide exchange, and 13Cα and 13Cβ secondary chemical shift data, it is shown that IL-4 consists offour long helices (residues 9-21, 45-64, 74-96, and 113-129), two small helical turns (residues 27-29 and 67-70), and a mini antiparallel β-sheet (residues 32-34 and 110-112). In addition, the topological arrangement of the helices and the global fold could be readily deduced from a number oflong-range interhelical NOEs identified in the 3D 13C-edited NOE spectrum in combination with the spatial restrictions imposed by three disulfide bridges. These data indicate that the helices ofinterleukin-4 are arranged in a left-handed four-helix bundle with two overhand connections.
AB - The secondary structure of human recombinant interleukin-4 (IL-4) has been investigated by three-dimensional (3D) 15N- and 13C-edited nuclear Overhauser (NOE) spectroscopy on the basis of the 1H, 15N, and 13C assignments presented in the preceding paper [Powers, R., Garrett, D. S., March, C. J., Frieden, E. A., Gronenborn, A. M., ' Clore, G. M., (1992) Biochemistry (preceding paper in this issue)]. Based on the NOE data involving the NH, CαH, and CβH protons, as well as 3JHnα coupling constant, amide exchange, and 13Cα and 13Cβ secondary chemical shift data, it is shown that IL-4 consists offour long helices (residues 9-21, 45-64, 74-96, and 113-129), two small helical turns (residues 27-29 and 67-70), and a mini antiparallel β-sheet (residues 32-34 and 110-112). In addition, the topological arrangement of the helices and the global fold could be readily deduced from a number oflong-range interhelical NOEs identified in the 3D 13C-edited NOE spectrum in combination with the spatial restrictions imposed by three disulfide bridges. These data indicate that the helices ofinterleukin-4 are arranged in a left-handed four-helix bundle with two overhand connections.
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U2 - 10.1021/bi00132a027
DO - 10.1021/bi00132a027
M3 - Article
C2 - 1567881
AN - SCOPUS:0026632791
VL - 31
SP - 4347
EP - 4353
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 17
ER -