000638192 001__ 638192
000638192 005__ 20250918134955.0
000638192 0247_ $$2doi$$a10.1021/acsomega.5c04764
000638192 037__ $$aPUBDB-2025-04010
000638192 082__ $$a660
000638192 1001_ $$00000-0002-6882-9910$$aMattiotti, Giovanni$$b0
000638192 245__ $$aStructural Implications of Missense Point Mutations in Shwachman–Bodian–Diamond Syndrome Protein (SBDS): A Combined SAXS/MD Investigation
000638192 260__ $$aWashington, DC$$bACS Publications$$c2025
000638192 3367_ $$2DRIVER$$aarticle
000638192 3367_ $$2DataCite$$aOutput Types/Journal article
000638192 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1758194261_3298674
000638192 3367_ $$2BibTeX$$aARTICLE
000638192 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000638192 3367_ $$00$$2EndNote$$aJournal Article
000638192 520__ $$aShwachman–Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by pleiotropic phenotypes, including pancreatic insufficiency, skeletal abnormalities, and bone marrow dysfunction. Notably, patients with SDS exhibit an increased risk of developing myelodysplastic syndrome and leukemia. In this study, we employed a combination of comparative molecular dynamics (MD) simulations and small-angle X-ray scattering (SAXS)-based analysis to investigate the Shwachman–Bodian–Diamond syndrome protein (SBDS). Specifically, we explored the molecular basis of the syndrome by examining the conformational dynamics of a set of missense mutants of SBDS in comparison to those of the wild-type (WT) protein. Our observations suggest that different mutations may impact (i) the interaction of SBDS with the ribosome, (ii) the binding of SBDS to Elongation Factor-Like 1 (EFL1), and (iii) the SBDS rearrangements coupled to EFL1 binding. Extensive MD simulations, with a total simulation time of 17 μs, revealed variations in the interdomain flexibility of SBDS, which are consistent with previously published affinity data and the new SAXS experimental data presented here. We propose a structural rationale behind the previously reported weak interaction of mutants I167T, R175W, and I212T with EFL1. Additionally, SAXS data indicate that R19Q, I167T, and R175W mutants exhibit altered relative abundances of SBDS conformational states in solution, further supporting our computational results. Overall, our integrated computational and experimental approach provides a comprehensive understanding of how specific mutations in SBDS alter its structural dynamics and binding interactions. These insights enhance our broader understanding of SBDS function and its role in ribosome biogenesis.
000638192 536__ $$0G:(DE-HGF)POF4-6G3$$a6G3 - PETRA III (DESY) (POF4-6G3)$$cPOF4-6G3$$fPOF IV$$x0
000638192 588__ $$aDataset connected to CrossRef, Journals: bib-pubdb1.desy.de
000638192 693__ $$0EXP:(DE-H253)P-P12-20150101$$1EXP:(DE-H253)PETRAIII-20150101$$6EXP:(DE-H253)P-P12-20150101$$aPETRA III$$fPETRA Beamline P12$$x0
000638192 7001_ $$0P:(DE-HGF)0$$aNanna, Vittoria$$b1
000638192 7001_ $$aGiulini, Marco$$b2
000638192 7001_ $$00000-0002-9475-9602$$aAlberga, Domenico$$b3
000638192 7001_ $$00000-0003-4042-2841$$aMangiatordi, Giuseppe Felice$$b4
000638192 7001_ $$00000-0002-8945-7001$$aSánchez-Puig, Nuria$$b5
000638192 7001_ $$00000-0001-5086-2459$$aSaviano, Michele$$b6
000638192 7001_ $$00000-0002-8767-2429$$aTubiana, Luca$$b7
000638192 7001_ $$00000-0001-6408-9380$$aPotestio, Raffaello$$b8
000638192 7001_ $$00000-0002-0808-6457$$aLattanzi, Gianluca$$b9$$eCorresponding author
000638192 7001_ $$00000-0003-1415-8725$$aSiliqi, Dritan$$b10$$eCorresponding author
000638192 773__ $$0PERI:(DE-600)2861993-6$$a10.1021/acsomega.5c04764$$gVol. 10, no. 31, p. 35103 - 35118$$n31$$p35103 - 35118$$tACS omega$$v10$$x2470-1343$$y2025
000638192 8564_ $$uhttps://pubs.acs.org/doi/full/10.1021/acsomega.5c04764
000638192 9131_ $$0G:(DE-HGF)POF4-6G3$$1G:(DE-HGF)POF4-6G0$$2G:(DE-HGF)POF4-600$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bForschungsbereich Materie$$lGroßgeräte: Materie$$vPETRA III (DESY)$$x0
000638192 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bACS OMEGA : 2022$$d2025-01-07
000638192 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-01-07
000638192 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2025-01-07
000638192 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-11-13T17:04:20Z
000638192 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-11-13T17:04:20Z
000638192 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2023-11-13T17:04:20Z
000638192 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2025-01-07
000638192 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2025-01-07
000638192 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-01-07
000638192 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2025-01-07
000638192 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2025-01-07
000638192 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2025-01-07
000638192 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2025-01-07
000638192 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2025-01-07
000638192 9201_ $$0I:(DE-H253)EMBL-User-20120814$$kEMBL-User$$lEMBL-User$$x0
000638192 980__ $$ajournal
000638192 980__ $$aEDITORS
000638192 980__ $$aVDBINPRINT
000638192 980__ $$aI:(DE-H253)EMBL-User-20120814
000638192 980__ $$aUNRESTRICTED