7bhe | pdb_00007bhe

DARPin_D5/Her3 domain 4 complex, monoclinic crystals

spinqualitylabelsall models 7bhe, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7bhe is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.297Å Ligands: ACT, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ERBB3_HUMAN Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2) [MIM:607598; also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord. The LCCS2 syndrome is characterized by multiple joint contractures, anterior horn atrophy in the spinal cord, and a unique feature of a markedly distended urinary bladder. The phenotype suggests a spinal cord neuropathic etiology. Function ERBB3_HUMAN Binds and is activated by neuregulins and NTAK. Publication Abstract from PubMed The members of the human epidermal growth factor receptor (HER) family are among the most intensely studied oncological targets. HER3 (ErbB3), which had long been neglected, has emerged as a key oncogene, regulating the activity of other receptors and being involved in progression and tumor escape in multiple types of cancer. Designed ankyrin-repeat proteins (DARPins) serve as antibody mimetics that have proven to be useful in the clinic, in diagnostics and in research. DARPins have previously been selected against EGFR (HER1), HER2 and HER4. In particular, their combination into bivalent binders that separate or lock receptors in their inactive conformation has proved to be a promising strategy for the design of potent anticancer therapeutics. Here, the selection of DARPins targeting extracellular domain 4 of HER3 (HER3d4) is described. One of the selected DARPins, D5, in complex with HER3d4 crystallized in two closely related crystal forms that diffracted to 2.3 and 2.0 A resolution, respectively. The DARPin D5 epitope comprises HER3d4 residues 568-577. These residues also contribute to interactions within the tethered (inactive) and extended (active) conformations of the extracellular domain of HER3. Crystal structures of HER3 extracellular domain 4 in complex with the designed ankyrin-repeat protein D5.,Radom F, Vonrhein C, Mittl PRE, Pluckthun A Acta Crystallogr F Struct Biol Commun. 2021 Jul 1;77(Pt 7):192-201. doi: , 10.1107/S2053230X21006002. Epub 2021 Jun 29. PMID:34196609 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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