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These peptides, along with their precursor, have been implicated in multiple pathophysiological roles, especially in neurodegenerative diseases. Previously we showed that GRN\u20103 and GRN\u20105 are fully disordered in the reduced form implicating redox sensitive attributes to the proteins. Redox\u2010based modulations are often carried out by metalloproteins in mitigating oxidative stress and maintaining metal\u2010homeostasis within cells. To probe whether GRNs play a role in metal sequestration, we tested the metal binding propensity of the reduced forms of GRNs \u22123 and\u2009\u2212\u20095 under neutral and acidic pH mimicking cytosolic and lysosomal conditions, respectively. We found, at neutral pH, both GRNs selectively bind Cu and no other divalent metal cations, with a greater specificity for Cu(I). Binding of Cu did not result in a disorder\u2010to\u2010order structural transition but partly triggered the multimerization of GRNs via uncoordinated cystines at both pH conditions. Overall, the results indicate that GRNs \u22123 and\u2009\u2212\u20095 have surprisingly strong affinity for Cu in the pM range, comparable to other known copper sequestering proteins. The results also hint at a potential of GRNs to reduce Cu(II) to Cu(I), a process that has significance in mitigating Cu\u2010induced ROS cytotoxicity in cells. Together, this report uncovers metal\u2010coordinating property of GRNs for the first time, which may have profound significance in their structure and pathophysiological functions.<\/jats:p>","DOI":"10.1002\/prot.26031","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T10:00:33Z","timestamp":1606730433000},"page":"450-461","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Are granulins copper sequestering proteins?"],"prefix":"10.1002","volume":"89","author":[{"given":"Anukool A.","family":"Bhopatkar","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry School of Mathematics and Natural Sciences and University of Southern Mississippi  Hattiesburg Mississippi 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