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To date, only two crystal structures of the BTB\/POZ\u2010KRP domains as tight dimers are available, which limits structure\u2010based predictions and interpretation of its role(s) in inducing clinical artemisinin resistance. Our solution Small\u2010Angle X\u2010ray Scattering (SAXS) data analysis and shape restoration brought forth that: (a) PfKelch13 forms a stable hexamer in P6 symmetry, (b) interactions of the N\u2010termini drive the hexameric assembly, and (c) the six KRP domains project independently in space, forming a cauldron\u2010like architecture. We further deduce that the artemisinin\u2010sensitive mutant A578S is packed like the wild\u2010type protein, however, hexameric assemblies of the predominant artemisinin\u2010resistant mutants R539T and C580Y displayed detectable differences in the spatial positioning of their BTB\/POZ\u2010KRP domains. Lastly, mapping of mutations known to enable artemisinin resistance suggested evolutionary pressure in the selection for mutations in the BTB\/POZ\u2010KRP domains. These mutations appear non\u2010detrimental to the hexameric assembly of proteins, and yet somehow alter the flux of downstream events essential for the susceptibility to artemisinin.\n                  <\/jats:p>","DOI":"10.1111\/febs.16378","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T20:09:15Z","timestamp":1643400555000},"page":"4935-4962","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<i>Plasmodium falciparum<\/i>\n                    Kelch13 and its artemisinin\u2010resistant mutants assemble as hexamers in solution: a SAXS data\u2010driven modelling study"],"prefix":"10.1111","volume":"289","author":[{"given":"Nainy","family":"Goel","sequence":"first","affiliation":[{"name":"Special Centre for Molecular Medicine Jawaharlal Nehru University  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanika","family":"Dhiman","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research\u2010Institute of Microbial Technology  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Kalidas","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research\u2010Institute of Microbial Technology  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwesha","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Special Centre for Molecular Medicine Jawaharlal Nehru University  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fnu","family":"Ashish","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research\u2010Institute of Microbial Technology  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3782-5677","authenticated-orcid":false,"given":"Souvik","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Special Centre for Molecular Medicine Jawaharlal Nehru University  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"World malaria report 2020.2020[https:\/\/www.who.int\/publications\/i\/item\/9789240015791]. 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