{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T18:16:56Z","timestamp":1782411416355,"version":"3.54.5"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T00:00:00Z","timestamp":1603670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001858","name":"VINNOVA","doi-asserted-by":"publisher","award":["2015\u201004912"],"award-info":[{"award-number":["2015\u201004912"]}],"id":[{"id":"10.13039\/501100001858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Machupo virus, known to cause hemorrhagic fevers, enters human cells via binding with its envelope glycoprotein to transferrin receptor 1 (TfR). Similarly, the receptor interactions have been explored in biotechnological applications as a molecular system to ferry therapeutics across the cellular membranes and through the impenetrable blood\u2013brain barrier that effectively blocks any such delivery into the brain. Study of the experimental structure of Machupo virus glycoprotein 1 (MGP1) in complex with TfR and glycoprotein sequence homology has identified some residues at the interface that influence binding. There are, however, no studies that have attempted to optimize the binding potential between MGP1 and TfR. In pursuits for finding therapeutic solutions for the New World arenaviruses, and to gain a greater understanding of MGP1 interactions with TfR, it is crucial to understand the structure\u2013sequence relationship driving the interface formation. By displaying MGP1 on yeast surface we have examined the contributions of individual residues to the binding of solubilized ectodomain of TfR. We identified MGP1 binding hot spot residues, assessed the importance of posttranslational <jats:italic>N<\/jats:italic>\u2010glycan modifications, and used a selection with random mutagenesis for affinity maturation. We show that the optimized MGP1 variants can bind more strongly to TfR than the native MGP1, and there is an MGP1 sequence that retains binding in the absence of glycosylation, but with the addition of further amino acid substitutions. The engineered variants can be used to probe cellular internalization or the blood\u2010brain barrier crossing to achieve greater understanding of TfR mediated internalization.<\/jats:p>","DOI":"10.1002\/prot.26016","type":"journal-article","created":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T10:11:05Z","timestamp":1602929465000},"page":"311-321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tuning the binding interface between Machupo virus glycoprotein and human transferrin receptor"],"prefix":"10.1002","volume":"89","author":[{"given":"Dick J","family":"Sj\u00f6str\u00f6m","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biomedical Sciences Linnaeus University  Kalmar Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneli","family":"Lundgren","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biomedical Sciences Linnaeus University  Kalmar Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J","family":"Garforth","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Albert Einstein College of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9300-614X","authenticated-orcid":false,"given":"Sinisa","family":"Bjelic","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biomedical Sciences Linnaeus University  Kalmar Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105786108"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.69.031905.164337"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913192107"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/47417"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.158"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0249-1"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2012.687719"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.04.026"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021398"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05539"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2842"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.5048"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401467200"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00130-8"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2019.106242"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-016-0405-9"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009835"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.25228"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2001.02073.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1307152110"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1772"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0697-553"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2007.08.012"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1202617"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2697(02)00018-0"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzq002"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.94"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1385\/MB:34:2:225"},{"key":"e_1_2_10_30_1","unstructured":"FlowJo\u2122 Software Version 10.5.0.[computer program]. 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