Crystal structure of the complex of diphtheria toxin with an extracellular fragment of its receptor.
We describe the crystal structure at 2.65 A resolution of diphtheria toxin (DT) complexed 1:1 with a fragment of its cell-surface receptor, the precursor of heparin-binding epidermal-growth-factor-like growth factor (HBEGF). HBEGF in the complex has the typical EGF-like fold and packs its principal beta hairpin against the face of a beta sheet in the receptor-binding domain of DT. The interface has a predominantly hydrophobic core, and polar interactions are formed at the periphery. The structure of the complex suggests that part of the membrane anchor of the receptor can interact with a hinge region of DT. The toxin molecule is thereby induced to form an open conformation conducive to membrane insertion. The structure provides a basis for altering the binding specificity of the toxin, and may also serve as a model for other EGF-receptor interactions.
Louie
G V
GV
Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Yang
W
W
Bowman
M E
ME
Choe
S
S
D001665:Binding Sites / Q000502:physiology; D003353:Corynebacterium diphtheriae / Q000737:chemistry*; D003461:Crystallography; D004167:Diphtheria Toxin / Q000737:chemistry* / Q000378:metabolism; D066246:ErbB Receptors / Q000737:chemistry; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007091:Image Processing, Computer-Assisted; D036341:Intercellular Signaling Peptides and Proteins; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism
D004167:Diphtheria Toxin; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D066246:ErbB Receptors