+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29044 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of Zanidatamab bound to HER2 | |||||||||
Map data | cryosparc refined map | |||||||||
Sample |
| |||||||||
Function / homology | Function and homology information negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / semaphorin receptor complex / regulation of microtubule-based process / ErbB-3 class receptor binding / Sema4D induced cell migration and growth-cone collapse ...negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / semaphorin receptor complex / regulation of microtubule-based process / ErbB-3 class receptor binding / Sema4D induced cell migration and growth-cone collapse / motor neuron axon guidance / neurotransmitter receptor localization to postsynaptic specialization membrane / PLCG1 events in ERBB2 signaling / positive regulation of Rho protein signal transduction / ERBB2-EGFR signaling pathway / neuromuscular junction development / ERBB2 Activates PTK6 Signaling / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / enzyme-linked receptor protein signaling pathway / positive regulation of transcription by RNA polymerase I / ERBB2-ERBB3 signaling pathway / oligodendrocyte differentiation / ERBB2 Regulates Cell Motility / semaphorin-plexin signaling pathway / PI3K events in ERBB2 signaling / positive regulation of protein targeting to membrane / positive regulation of cell adhesion / regulation of angiogenesis / coreceptor activity / Schwann cell development / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / myelination / Downregulation of ERBB2:ERBB3 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / GRB2 events in ERBB2 signaling / transmembrane receptor protein tyrosine kinase activity / neurogenesis / SHC1 events in ERBB2 signaling / Constitutive Signaling by Overexpressed ERBB2 / basal plasma membrane / regulation of ERK1 and ERK2 cascade / positive regulation of translation / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of epithelial cell proliferation / Signaling by ERBB2 TMD/JMD mutants / neuromuscular junction / positive regulation of MAP kinase activity / wound healing / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / receptor tyrosine kinase binding / receptor protein-tyrosine kinase / neuron differentiation / cellular response to growth factor stimulus / ruffle membrane / Downregulation of ERBB2 signaling / peptidyl-tyrosine phosphorylation / cell surface receptor protein tyrosine kinase signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / transmembrane signaling receptor activity / PIP3 activates AKT signaling / presynaptic membrane / myelin sheath / heart development / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / positive regulation of cell growth / basolateral plasma membrane / protein tyrosine kinase activity / positive regulation of MAPK cascade / cell surface receptor signaling pathway / receptor complex / early endosome / endosome membrane / intracellular signal transduction / positive regulation of protein phosphorylation / apical plasma membrane / protein heterodimerization activity / signaling receptor binding / protein phosphorylation / positive regulation of cell population proliferation / negative regulation of apoptotic process / perinuclear region of cytoplasm / signal transduction / nucleoplasm / ATP binding / membrane / identical protein binding / nucleus / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 7.5 Å | |||||||||
Authors | Worrall LJ / Atkinson CE / Sanches M / Dixit S / Strynadka NCJ | |||||||||
Funding support | Canada, 1 items
| |||||||||
Citation | Journal: To be Published Title: Zanidatamab, an Anti-HER2 Biparatopic that Induces Unique Surface HER2 Clusters and Complement-Dependent Cytotoxicity Authors: Weisser N / Wickman G / Sanches M / Escobar-Cabrera E / O'Toole J / Abraham L / Guedia J / Baichoo P / Volkers G / Schrag J / Choi K / Grothe S / Baardsnes J / Worrall LJ / Atkinson CE / ...Authors: Weisser N / Wickman G / Sanches M / Escobar-Cabrera E / O'Toole J / Abraham L / Guedia J / Baichoo P / Volkers G / Schrag J / Choi K / Grothe S / Baardsnes J / Worrall LJ / Atkinson CE / Harbourne B / Cheng CW / Whalen E / Smith J / Zwierzchowski P / Zwaagstra J / Jolicoeur N / Lippens J / Fung V / Black S / Dargahi D / Samiotakis A / Chan P / Stevens C / Farber P / Mukhopadhyay A / Browman D / Strynadka NCJ / Gold MR / Dixit S | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_29044.map.gz | 59.7 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-29044-v30.xml emd-29044.xml | 18.9 KB 18.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_29044_fsc.xml | 8.4 KB | Display | FSC data file |
Images | emd_29044.png | 56.2 KB | ||
Others | emd_29044_half_map_1.map.gz emd_29044_half_map_2.map.gz | 59.4 MB 59.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29044 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29044 | HTTPS FTP |
-Related structure data
Related structure data | 8ffjMC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_29044.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | cryosparc refined map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.4 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: cryosparc refined half map
File | emd_29044_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | cryosparc refined half map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: cryosparc refined half map
File | emd_29044_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | cryosparc refined half map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Complex of Zanidatamab and HER2
Entire | Name: Complex of Zanidatamab and HER2 |
---|---|
Components |
|
-Supramolecule #1: Complex of Zanidatamab and HER2
Supramolecule | Name: Complex of Zanidatamab and HER2 / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Receptor tyrosine-protein kinase erbB-2
Macromolecule | Name: Receptor tyrosine-protein kinase erbB-2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: receptor protein-tyrosine kinase |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 68.536844 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: TQVCTGTDMK LRLPASPETH LDMLRHLYQG CQVVQGNLEL TYLPTNASLS FLQDIQEVQG YVLIAHNQVR QVPLQRLRIV RGTQLFEDN YALAVLDNGD PLNNTTPVTG ASPGGLRELQ LRSLTEILKG GVLIQRNPQL CYQDTILWKD IFHKNNQLAL T LIDTNRSR ...String: TQVCTGTDMK LRLPASPETH LDMLRHLYQG CQVVQGNLEL TYLPTNASLS FLQDIQEVQG YVLIAHNQVR QVPLQRLRIV RGTQLFEDN YALAVLDNGD PLNNTTPVTG ASPGGLRELQ LRSLTEILKG GVLIQRNPQL CYQDTILWKD IFHKNNQLAL T LIDTNRSR ACHPCSPMCK GSRCWGESSE DCQSLTRTVC AGGCARCKGP LPTDCCHEQC AAGCTGPKHS DCLACLHFNH SG ICELHCP ALVTYNTDTF ESMPNPEGRY TFGASCVTAC PYNYLSTDVG SCTLVCPLHN QEVTAEDGTQ RCEKCSKPCA RVC YGLGME HLREVRAVTS ANIQEFAGCK KIFGSLAFLP ESFDGDPASN TAPLQPEQLQ VFETLEEITG YLYISAWPDS LPDL SVFQN LQVIRGRILH NGAYSLTLQG LGISWLGLRS LRELGSGLAL IHHNTHLCFV HTVPWDQLFR NPHQALLHTA NRPED ECVG EGLACHQLCA RGHCWGPGPT QCVNCSQFLR GQECVEECRV LQGLPREYVN ARHCLPCHPE CQPQNGSVTC FGPEAD QCV ACAHYKDPPF CVARCPSGVK PDLSYMPIWK FPDEEGACQP CPINCTHSCV DLDDKGCPA |
-Macromolecule #2: Zanidatamab Heavy Chain A
Macromolecule | Name: Zanidatamab Heavy Chain A / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 49.217211 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: GEVQLVESGG GLVQPGGSLR LSCAASGFTF TDYTMDWVRQ APGKGLEWVA DVNPNSGGSI YNQRFKGRFT LSVDRSKNTL YLQMNSLRA EDTAVYYCAR NLGPSFYFDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String: GEVQLVESGG GLVQPGGSLR LSCAASGFTF TDYTMDWVRQ APGKGLEWVA DVNPNSGGSI YNQRFKGRFT LSVDRSKNTL YLQMNSLRA EDTAVYYCAR NLGPSFYFDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSCDKTHT CPPCPAPELL GG PSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE QYNSTYRVVS VLTVLHQDWL NGK EYKCKV SNKALPAPIE KTISKAKGQP REPQVYVYPP SRDELTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPV LDSDG SFALVSKLTV DKSRWQQGNV FSCSVMHEAL HNHYTQKSLS LSPGGS |
-Macromolecule #3: Zanidatamab Light Chain A
Macromolecule | Name: Zanidatamab Light Chain A / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.749334 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: GDIQMTQSPS SLSASVGDRV TITCKASQDV SIGVAWYQQK PGKAPKLLIY SASYRYTGVP SRFSGSGSGT DFTLTISSLQ PEDFATYYC QQYYIYPYTF GQGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: GDIQMTQSPS SLSASVGDRV TITCKASQDV SIGVAWYQQK PGKAPKLLIY SASYRYTGVP SRFSGSGSGT DFTLTISSLQ PEDFATYYC QQYYIYPYTF GQGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGECGS |
-Macromolecule #4: Zanidatamab Heavy Chain B
Macromolecule | Name: Zanidatamab Heavy Chain B / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 52.5415 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: GDIQMTQSPS SLSASVGDRV TITCRASQDV NTAVAWYQQK PGKAPKLLIY SASFLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQHYTTPPTF GQGTKVEIKG GSGGGSGGGS GGGSGGGSGE VQLVESGGGL VQPGGSLRLS CAASGFNIKD T YIHWVRQA ...String: GDIQMTQSPS SLSASVGDRV TITCRASQDV NTAVAWYQQK PGKAPKLLIY SASFLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQHYTTPPTF GQGTKVEIKG GSGGGSGGGS GGGSGGGSGE VQLVESGGGL VQPGGSLRLS CAASGFNIKD T YIHWVRQA PGKGLEWVAR IYPTNGYTRY ADSVKGRFTI SADTSKNTAY LQMNSLRAED TAVYYCSRWG GDGFYAMDYW GQ GTLVTVS SAAEPKSSDK THTCPPCPAP ELLGGPSVFL FPPKPKDTLM ISRTPEVTCV VVDVSHEDPE VKFNWYVDGV EVH NAKTKP REEQYNSTYR VVSVLTVLHQ DWLNGKEYKC KVSNKALPAP IEKTISKAKG QPREPQVYVL PPSRDELTKN QVSL LCLVK GFYPSDIAVE WESNGQPENN YLTWPPVLDS DGSFFLYSKL TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSP GGS |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 4.0 µm / Nominal defocus min: 1.0 µm |
Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: INTEGRATING / Average electron dose: 110.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |