{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:22:44Z","timestamp":1760059364918,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-74-10008"],"award-info":[{"award-number":["24-74-10008"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We investigated the interaction of HspB7 and its \u03b1-crystallin domain with the wild-type (WT) C-terminal fragment of human filamin C (FLNC), containing immunoglobulin-like domains 22\u201324 and its three mutants associated with cardio- and myopathies. The physicochemical properties of the WT FLNC fragment and its three mutants, p.Glu2472_Asn2473delinsAsp (EN\/D) located in the 22nd domain, p.P2643_L2645del (\u0394PGL), and p.W2710X (Wmut) both located in the 24th immunoglobulin-like domain were analyzed. Although all FLNC fragments had similar secondary structures, WT FLNC and its EN\/D and \u0394PGL mutants formed dimers, whereas Wmut formed either monomers or aggregates. The surface hydrophobicity of EN\/D, \u0394PGL, and especially Wmut mutants was larger than that of the WT fragment. Size exclusion chromatography, native gel electrophoresis, and chemical crosslinking indicated that the efficiency of interaction with HspB7 or its \u03b1-crystallin domain decreased in the order WT~EN\/D &gt; \u0394PGL. Wmut was unable to interact with either HspB7 or its \u03b1-crystallin domain. Modeling via Alphafold 3 indicated that EN\/D mutation affected the orientation of two loops connecting \u03b2-strands in the 22nd domain, while the \u0394PGL and Wmut mutations exposed a hydrophobic groove in the 24th domain thereby reducing their interaction with HspB7. These findings reveal the molecular mechanisms underlying filaminopathies associated with three mutations in the C-terminal region of filamin C.<\/jats:p>","DOI":"10.3390\/ijms26125512","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:46:01Z","timestamp":1749451561000},"page":"5512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Mutations in the C-Terminal 22\u201324 Domains of Filamin C Associated with Cardio- and Myopathies on Its Interaction with Small Heat Shock Protein HspB7"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4170-3071","authenticated-orcid":false,"given":"Lydia K.","family":"Muranova","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Biology, Lomonosov Moscow State University, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varvara M.","family":"Vostrikova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Biology, Lomonosov Moscow State University, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9779-6273","authenticated-orcid":false,"given":"Nikolai B.","family":"Gusev","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Biology, Lomonosov Moscow State University, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.tcb.2009.12.001","article-title":"Filamins in cell signaling, transcription and organ development","volume":"20","author":"Zhou","year":"2010","journal-title":"Trends Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1143858","DOI":"10.3389\/fphys.2023.1143858","article-title":"Structural and signaling proteins in the Z-disk and their role in cardiomyopathies","volume":"14","author":"Noureddine","year":"2023","journal-title":"Front. 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