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Capsid Assembly Modulators (CAMs) are direct acting antivirals that induce HBc mis-assembly and are the subject of active research and development. Two versions of HBc are used in structural studies of CAM-HBc complexes: Cp150 and Cp149-Y132A. Cp150 forms empty icosahedral capsids that are structurally indistinguishable from those found in virions. The Y132A mutation of Cp149 leads to an assembly defective soluble protein that crystalizes as flat hexagonal sheets, where the hexagons resemble icosahedral quasi-sixfold vertices. In this study, we compare structures of CAM-bound Cp150 to CAM-bound Cp149-Y132A. In capsids, the residues forming the CAM site shift to match the structure of bound CAMs, an induced fit. In Cp149-Y132A crystals, CAM sites show little structural adjustment in response to different CAMs binding. In turn, the array of residues that interact with CAMs varies from CAM to CAM in capsid structures but remains nearly constant in Cp149-Y132A crystals. These results illustrate important differences between CAM binding in Cp149-Y132A and Cp150 structures that will contribute to future CAM design.<\/jats:p>","DOI":"10.64898\/2026.05.13.724798","type":"posted-content","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T15:26:01Z","timestamp":1778772361000},"source":"Crossref","is-referenced-by-count":0,"title":["Assembly-active and -inactive forms of HBV capsid protein provide distinctly different binding sites for capsid assembly modulators"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-5676","authenticated-orcid":false,"given":"Liam W.","family":"Scott","sequence":"first","affiliation":[{"name":"Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN 47405 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8766-789X","authenticated-orcid":false,"given":"Carolina","family":"P\u00e9rez-Segura","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware 19716, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4685-8291","authenticated-orcid":false,"given":"Jodi A.","family":"Hadden-Perilla","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware 19716, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Zlotnick","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN 47405 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026051621400689000_2026.05.13.724798v1.1","unstructured":"Organization, W.W.H., Global hepatitis report 2024: action for access in low- and middle-income countries, W.H. 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