6S9J

Crystal structure of TfR1 mimicry in complex with GP1 from MACV

Summary for 6S9J

• Entry DOI: 10.2210/pdb6s9j/pdb
• Descriptor: Pre-glycoprotein polyprotein GP complex, Transferrin receptor 1,Transferrin receptor 1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: immunotherapy, glycoprotein, viral, viral protein
• Biological source: Machupo virus (MACV); More
• Total number of polymer chains: 8
• Total formula weight: 157978.86

Authors

Diskin, R.,Cohen-Dvashi, H. (deposition date: 2019-07-15, release date: 2020-01-15, Last modification date: 2024-11-06)

Primary citation

Cohen-Dvashi, H.,Amon, R.,Agans, K.N.,Cross, R.W.,Borenstein-Katz, A.,Mateo, M.,Baize, S.,Padler-Karavani, V.,Geisbert, T.W.,Diskin, R.
Rational design of universal immunotherapy for TfR1-tropic arenaviruses.
Nat Commun, 11:67-67, 2020

PubMed Abstract: Certain arenaviruses that circulate in rodent populations can cause life-threatening hemorrhagic fevers when they infect humans. Due to their efficient transmission, arenaviruses pose a severe risk for outbreaks and might be exploited as biological weapons. Effective countermeasures against these viruses are highly desired. Ideally, a single remedy would be effective against many or even all the pathogenic viruses in this family. However, despite the fact that all pathogenic arenaviruses from South America utilize transferrin receptor 1 (TfR1) as a cellular receptor, their viral glycoproteins are highly diversified, impeding efforts to isolate cross-neutralizing antibodies. Here we address this problem using a rational design approach to target TfR1-tropic arenaviruses with high potency and breadth. The pan-reactive molecule is highly effective against all arenaviruses that were tested, offering a universal therapeutic approach. Our design scheme avoids the shortcomings of previous immunoadhesins and can be used to combat other zoonotic pathogens.

PubMed: 31900422
DOI: 10.1038/s41467-019-13924-6

Experimental method

X-RAY DIFFRACTION (2.698 Å)