6eqc
From Proteopedia
Cryo-EM reconstruction of a complex of a binding protein and human adenovirus C5 hexon
Structural highlights
Function[CAPSH_ADE05] Major capsid protein that self-associates to form 240 hexon trimers, each in the shape of a hexagon, building most of the pseudo T=25 capsid. Assembled into trimeric units with the help of the chaperone shutoff protein (By similarity). Transported by pre-protein VI to the nucleus where it associates with other structural proteins to form an empty capsid. Might be involved, through its interaction with host dyneins, in the intracellular microtubule-dependent transport of incoming viral capsid to the nucleus. Publication Abstract from PubMedMost systemic viral gene therapies have been limited by sequestration and degradation of virions, innate and adaptive immunity, and silencing of therapeutic genes within the target cells. Here we engineer a high-affinity protein coat, shielding the most commonly used vector in clinical gene therapy, human adenovirus type 5. Using electron microscopy and crystallography we demonstrate a massive coverage of the virion surface through the hexon-shielding scFv fragment, trimerized to exploit the hexon symmetry and gain avidity. The shield reduces virion clearance in the liver. When the shielded particles are equipped with adaptor proteins, the virions deliver their payload genes into human cancer cells expressing HER2 or EGFR. The combination of shield and adapter also increases viral gene delivery to xenografted tumors in vivo, reduces liver off-targeting and immune neutralization. Our study highlights the power of protein engineering for viral vectors overcoming the challenges of local and systemic viral gene therapies. Adenoviral vector with shield and adapter increases tumor specificity and escapes liver and immune control.,Schmid M, Ernst P, Honegger A, Suomalainen M, Zimmermann M, Braun L, Stauffer S, Thom C, Dreier B, Eibauer M, Kipar A, Vogel V, Greber UF, Medalia O, Pluckthun A Nat Commun. 2018 Jan 31;9(1):450. doi: 10.1038/s41467-017-02707-6. PMID:29386504[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found See AlsoReferences
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Categories: Human adenovirus 5 | Large Structures | Lk3 transgenic mice | Braun, L | Dreier, B | Eibauer, M | Ernst, P | Greber, U F | Honegger, A | Kipar, A | Medalia, O | Plueckthun, A | Schmid, M | Stauffer, S | Suomalainen, M | Thom, C | Vogel, V | Zimmermann, M | Antibody | Gene therapy viral protein | Human adenovirus c5 | Viral protein
