Oligomerization Function of the Native Exon 5 Sequence of Ameloblastin Fused with Calmodulin
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00617628" target="_blank" >RIV/61388963:_____/25:00617628 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/25:10494887 RIV/00216208:11320/25:10494887 RIV/62690094:18470/25:50022387
Result on the web
<a href="https://doi.org/10.1021/acsomega.4c07953" target="_blank" >https://doi.org/10.1021/acsomega.4c07953</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsomega.4c07953" target="_blank" >10.1021/acsomega.4c07953</a>
Alternative languages
Result language
angličtina
Original language name
Oligomerization Function of the Native Exon 5 Sequence of Ameloblastin Fused with Calmodulin
Original language description
The evolution of proteins is primarily driven by the combinatorial assembly of a limited set of pre-existing modules known as protein domains. This modular architecture not only supports the diversity of natural proteins but also provides a robust strategy for protein engineering, enabling the design of artificial proteins with enhanced or novel functions for various industrial applications. Among these functions, oligomerization plays a crucial role in enhancing protein activity, such as by increasing the binding capacity of antibodies. To investigate the potential of engineering oligomerization, we examined the transferability of the sequence domain encoded by exon 5 (Ex5), which was originally responsible for the oligomerization of ameloblastin (AMBN). We designed a two-domain protein composed of Ex5 in combination with a monomeric, globular, and highly stable protein, specifically calmodulin (CaM). CaM represents the opposite protein character to AMBN, which is highly disordered and has a dynamic character. This engineered protein, termed eCaM, successfully acquired an oligomeric function, inducing self-assembly under specific conditions. Biochemical and biophysical analyses revealed that the oligomerization of eCaM is both concentration- and time-dependent, with the process being reversible upon dilution. Furthermore, mutating a key oligomerization residue within Ex5 abolished the self-assembly of eCaM, confirming the essential role of the Ex5 motif in driving oligomerization. Our findings demonstrate that the oligomerization properties encoded by Ex5 can be effectively transferred to a new protein context, though the positioning of Ex5 within the protein structure is critical. This work highlights the potential of enhancing monomeric proteins with oligomeric functions, paving the way for industrial applications and the development of proteins with tailored properties.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA22-03875S" target="_blank" >GA22-03875S: Role of acute myeloid leukemia-associated nucleophosmin mutations in the NPM-p53-Mdm2 regulatory network</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS Omega
ISSN
2470-1343
e-ISSN
2470-1343
Volume of the periodical
10
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
7741-7751
UT code for WoS article
001427030400001
EID of the result in the Scopus database
2-s2.0-86000374671