1xdt
COMPLEX OF DIPHTHERIA TOXIN AND HEPARIN-BINDING EPIDERMAL GROWTH FACTORCOMPLEX OF DIPHTHERIA TOXIN AND HEPARIN-BINDING EPIDERMAL GROWTH FACTOR
Structural highlights
Function[DTX_CORBE] Diphtheria toxin, produced by a phage infecting Corynebacterium diphtheriae, is a proenzyme that, after activation, catalyzes the covalent attachment of the ADP ribose moiety of NAD to eukaryotic elongation factor 2 (eEF-2). Fragment A is the catalytic portion responsible for enzymatic ADP-ribosylation of elongation factor 2, while fragment B is responsible for binding of toxin to cell receptors and entry of fragment A.[1] [2] [HBEGF_HUMAN] Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4. Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe 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. Crystal structure of the complex of diphtheria toxin with an extracellular fragment of its receptor.,Louie GV, Yang W, Bowman ME, Choe S Mol Cell. 1997 Dec;1(1):67-78. PMID:9659904[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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