{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:53:36Z","timestamp":1788821616596,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01GM129854"],"award-info":[{"award-number":["R01GM129854"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32 GM067555"],"award-info":[{"award-number":["T32 GM067555"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UCLA Graduate Division Dissertation Year Fellowship","award":["R01GM129854"],"award-info":[{"award-number":["R01GM129854"]}]},{"name":"UCLA Graduate Division Dissertation Year Fellowship","award":["T32 GM067555"],"award-info":[{"award-number":["T32 GM067555"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Beta-2 microglobulin (B2M) is an immune system protein that is found on the surface of all nucleated human cells. B2M is naturally shed from cell surfaces into the plasma, followed by renal excretion. In patients with impaired renal function, B2M will accumulate in organs and tissues leading to significantly reduced life expectancy and quality of life. While current hemodialysis methods have been successful in managing electrolyte as well as small and large molecule disturbances arising in chronic renal failure, they have shown only modest success in managing plasma levels of B2M and similar sized proteins, while sparing important proteins such as albumin. We describe a systematic protein design effort aimed at adding the ability to selectively remove specific, undesired waste proteins such as B2M from the plasma of chronic renal failure patients. A novel nanoparticle built using a tetrahedral protein assembly as a scaffold that presents 12 copies of a B2M-binding nanobody is described. The designed nanoparticle binds specifically to B2M through protein\u2013protein interactions with nanomolar binding affinity (~4.2 nM). Notably, binding to the nanoparticle increases the effective size of B2M by over 50-fold, offering a potential selective avenue for separation based on size. We present data to support the potential utility of such a nanoparticle for removing B2M from plasma by either size-based filtration or by polyvalent binding to a stationary matrix under blood flow conditions. Such applications could address current shortcomings in the management of problematic mid-sized proteins in chronic renal failure patients.<\/jats:p>","DOI":"10.3390\/biom13071122","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:28:06Z","timestamp":1689294486000},"page":"1122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Design of Beta-2 Microglobulin Adsorbent Protein Nanoparticles"],"prefix":"10.3390","volume":"13","author":[{"given":"Justin E.","family":"Miller","sequence":"first","affiliation":[{"name":"Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3985-6194","authenticated-orcid":false,"given":"Roger","family":"Castells-Graells","sequence":"additional","affiliation":[{"name":"UCLA-DOE Institute for Genomics and Proteomics, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Arbing","sequence":"additional","affiliation":[{"name":"UCLA-DOE Institute for Genomics and Proteomics, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Munoz","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Xiao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlize T.","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1039-6614","authenticated-orcid":false,"given":"Brian","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Moroz","sequence":"additional","affiliation":[{"name":"School of Medicine, Curtin University, Perth, WA 6845, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5709-9839","authenticated-orcid":false,"given":"Todd O.","family":"Yeates","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA"},{"name":"UCLA-DOE Institute for Genomics and Proteomics, Los Angeles, CA 90095, USA"},{"name":"Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000479252","article-title":"Middle-Molecule Uremic Toxins and Outcomes in Chronic Kidney Disease","volume":"Volume 191","author":"Ronco","year":"2017","journal-title":"Contributions to Nephrology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.molcel.2010.11.028","article-title":"Conformational Conversion during Amyloid Formation at Atomic Resolution","volume":"41","author":"Eichner","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4517","DOI":"10.1038\/s41467-018-06761-6","article-title":"The Structure of a \u03922-Microglobulin Fibril Suggests a Molecular Basis for Its Amyloid Polymorphism","volume":"9","author":"Iadanza","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1053\/j.arrt.2003.11.003","article-title":"Beta-2 Microglobulin in ESRD: An in-Depth Review","volume":"10","author":"Winchester","year":"2003","journal-title":"Adv. Ren. Replace. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1440-1827.2001.01156.x","article-title":"Pathogenesis of \u03b22-microglobulin Amyloidosis","volume":"51","author":"Ohashi","year":"2001","journal-title":"Pathol. Int."},{"key":"ref_6","first-page":"153","article-title":"Clearance and Synthesis Rates of Beta 2-Microglobulin in Patients Undergoing Hemodialysis and in Normal Subjects","volume":"118","author":"Floege","year":"1991","journal-title":"J. Lab. Clin. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1093\/ckj\/sfy056","article-title":"Using the Newer Kidney Disease: Improving Global Outcomes Criteria, Beta-2-Microglobulin Levels Associate with Severity of Acute Kidney Injury","volume":"11","author":"Barton","year":"2018","journal-title":"Clin. Kidney J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.34067\/KID.0004922020","article-title":"Beta-2 Microglobulin Amyloidosis: Past, Present, and Future","volume":"1","author":"Yee","year":"2020","journal-title":"Kidney360"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1744-9987.1998.tb00067.x","article-title":"New Adsorption Column (Lixelle) to Eliminate Beta2-Microglobulin for Direct Hemoperfusion","volume":"2","author":"Furuyoshi","year":"1998","journal-title":"Ther. Apher."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"iii12","DOI":"10.1093\/ndt\/gfy224","article-title":"Current Approaches to Middle Molecule Removal: Room for Innovation","volume":"33","author":"Masakane","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1159\/000086207","article-title":"Assessment of the Stability of an Immunoadsorbent for the Extracorporeal Removal of Beta-2-Microglobulin from Blood","volume":"23","author":"Daniels","year":"2005","journal-title":"Blood Purif."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhang, L., Zang, B., Huang, C., Ren, J., and Jia, L. (2019). One-Step Preparation of a VHH-Based Immunoadsorbent for the Extracorporeal Removal of \u03922-Microglobulin. Molecules, 24.","DOI":"10.3390\/molecules24112119"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.actbio.2020.02.028","article-title":"Nanobody-Based High-Performance Immunosorbent for Selective Beta 2-Microglobulin Purification from Blood","volume":"107","author":"Huang","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/btpr.562","article-title":"Removal of Intact \u03922-Microglobulin at Neutral Ph by Using Seed-Conjugated Polymer Beads Prepared with \u03922-Microglobulin-Derived Peptide (58\u201367)","volume":"27","author":"Kang","year":"2011","journal-title":"Biotechnol. Prog."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1523-1755.2004.00377.x","article-title":"Single-Chain Antibody Fragment-Based Adsorbent for the Extracorporeal Removal of Beta2-Microglobulin","volume":"65","author":"Grovender","year":"2004","journal-title":"Kidney Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.pep.2005.01.016","article-title":"Protein Production by Auto-Induction in High Density Shaking Cultures","volume":"41","author":"Studier","year":"2005","journal-title":"Protein Expr. Purif."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9771","DOI":"10.1073\/pnas.152337399","article-title":"Crystal Structure of Monomeric Human \u03b2-2-Microglobulin Reveals Clues to Its Amyloidogenic Properties","volume":"99","author":"Trinh","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8735","DOI":"10.1021\/bi000276j","article-title":"Partially Unfolded States of \u03b22-Microglobulin and Amyloid Formation in Vitro","volume":"39","author":"McParland","year":"2000","journal-title":"Biochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.sbi.2019.03.008","article-title":"High-Symmetry Protein Assemblies: Patterns and Emerging Applications","volume":"55","author":"Cannon","year":"2019","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10439","DOI":"10.1021\/jacs.8b06442","article-title":"Rational Engineering of a Designed Protein Cage for SiRNA Delivery","volume":"140","author":"Edwardson","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature25157","article-title":"Evolution of a Designed Protein Assembly Encapsulating Its Own RNA Genome","volume":"552","author":"Butterfield","year":"2017","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5410","DOI":"10.1038\/s41467-020-19112-1","article-title":"Two-Tier Supramolecular Encapsulation of Small Molecules in a Protein Cage","volume":"11","author":"Edwardson","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eabd9994","DOI":"10.1126\/science.abd9994","article-title":"Designed Proteins Assemble Antibodies into Modular Nanocages","volume":"372","author":"Divine","year":"2021","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1021\/acssynbio.9b00407","article-title":"Designed Protein Cages as Scaffolds for Building Multienzyme Materials","volume":"9","author":"McConnell","year":"2020","journal-title":"ACS Synth. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nature12202","article-title":"Self-Assembling Influenza Nanoparticle Vaccines Elicit Broadly Neutralizing H1N1 Antibodies","volume":"499","author":"Kanekiyo","year":"2013","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.cell.2019.01.046","article-title":"Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus","volume":"176","author":"Marcandalli","year":"2019","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1021\/bm5014469","article-title":"Recent Advances in Engineering Polyvalent Biological Interactions","volume":"16","author":"Varner","year":"2015","journal-title":"Biomacromolecules"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/pro.3802","article-title":"Design and Structure of Two New Protein Cages Illustrate Successes and Ongoing Challenges in Protein Engineering","volume":"29","author":"Cannon","year":"2020","journal-title":"Protein Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1126\/science.aaf8818","article-title":"Accurate Design of Megadalton-Scale Two-Component Icosahedral Protein Complexes","volume":"353","author":"Bale","year":"2016","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1073\/pnas.1008560108","article-title":"Atomic Structure of a Nanobody-Trapped Domain-Swapped Dimer of an Amyloidogenic \u03922-Microglobulin Variant","volume":"108","author":"Domanska","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/j.chom.2022.10.018","article-title":"Lassa Virus Glycoprotein Nanoparticles Elicit Neutralizing Antibody Responses and Protection","volume":"30","author":"Brouwer","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1038\/s41467-019-09836-0","article-title":"A 3.8\u2009\u00c5 Resolution Cryo-EM Structure of a Small Protein Bound to an Imaging Scaffold","volume":"10","author":"Liu","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9145","DOI":"10.1021\/acs.chemrev.1c00877","article-title":"Protein Cages: From Fundamentals to Advanced Applications","volume":"122","author":"Edwardson","year":"2022","journal-title":"Chem. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9343","DOI":"10.1007\/s00253-013-5232-z","article-title":"Streptavidin-Biotin Technology: Improvements and Innovations in Chemical and Biological Applications","volume":"97","author":"Dundas","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/7\/1122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:11:43Z","timestamp":1760127103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/7\/1122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,14]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["biom13071122"],"URL":"https:\/\/doi.org\/10.3390\/biom13071122","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,14]]}}}