DC pole | Wartość | Język |
dc.contributor.author | Sieroń, Łukasz | - |
dc.contributor.author | Lesiak, Marta | - |
dc.contributor.author | Schisler, Izabela | - |
dc.contributor.author | Drzazga, Zofia | - |
dc.contributor.author | Fertala, Andrzej | - |
dc.contributor.author | Sieroń, Aleksander | - |
dc.date.accessioned | 2019-01-31T12:46:51Z | - |
dc.date.available | 2019-01-31T12:46:51Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Bioscience Reports, Vol. 39, iss. 1 (2019), Art. No. BSR20180270 | pl_PL |
dc.identifier.issn | 1573-4935 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.12128/8063 | - |
dc.description.abstract | Inactive mammalian tolloid-like 1 (tll1) and mutations detected in tolloid-like 1 (TLL1) have
been linked to the lack of the heart septa formation in mice and to a similar human inborn
condition called atrial-septal defect 6 (ASD6; OMIM 613087, formerly ASD II). Previously, we
reported four point mutations in TLL1 found in approximately 20% of ASD6 patients. Three
mutations in the coding sequence were M182L, V238A, and I629V. In this work, we present
the effects of these mutations on TLL1 function. Three recombinant cDNA constructs carrying
the mutations and onewild-type construct were prepared and then expressed in HT-1080
cells. Corresponding recombinant proteins were analyzed for their metalloendopeptidase
activity using a native substrate, chordin. The results of these assays demonstrated that in
comparison with the native TLL1, mutants cleaved chordin and procollagen I at significantly
lower rates. CD analyses revealed significant structural differences between the higher order
structure of wild-type and mutant variants. Moreover, biosensor-based assays of binding interactions
between TLL1 variants and chordin demonstrated a significant decrease in the
binding affinities of the mutated variants. The results from this work indicate that mutations
detected in TLL1 of ASD6 patients altered its metalloendopeptidase activity, structure, and
substrate-binding properties, thereby suggesting a possible pathomechanism of ASD6. | pl_PL |
dc.language.iso | en | pl_PL |
dc.rights | Uznanie autorstwa 3.0 Polska | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/pl/ | * |
dc.subject | tolloid-like 1 | pl_PL |
dc.subject | mutants | pl_PL |
dc.subject | atrial-septal defect 6 | pl_PL |
dc.title | Functional and structural studies of tolloid-like 1 mutants associated with atrial-septal defect 6 | pl_PL |
dc.type | info:eu-repo/semantics/article | pl_PL |
dc.relation.journal | Bioscience Reports | pl_PL |
dc.identifier.doi | 10.1042/BSR20180270 | - |
Pojawia się w kolekcji: | Artykuły (WNŚiT)
|