Computational Insights into the Structural and Functional Impacts of nsSNPs of Bone Morphogenetic Proteins.

Publisher: Hindawi Pub. Co Country of Publication: United States NLM ID: 101600173 Publication Model: eCollection Cited Medium: Internet ISSN: 2314-6141 (Electronic) NLM ISO Abbreviation: Biomed Res Int Subsets: MEDLINE

Original Publication: New York, NY : Hindawi Pub. Co.

Bone Morphogenetic Proteins*/metabolism ; Signal Transduction*; Binding Sites/genetics ; Mutation/genetics ; Transforming Growth Factor beta/genetics ; Transforming Growth Factor beta/metabolism

BMPs (bone morphogenetic proteins) are multipurpose (transforming growth factor)TGF-superfamily released cytokines. These glycoproteins, acting as disulfide-linked homo- or heterodimers, are highly potent regulators of bone and cartilage production and repair, cell proliferation throughout embryonic development, and bone homeostasis in the adults. Due to the fact that genetic variation might influence structural functions, this study is aimed to determine the pathogenic effect of nonsynonymous single-nucleotide polymorphisms (nsSNPs) in BMP genes. The implications of these variations, investigated using computational analysis and molecular models of the mature TGF- β domain, revealed the impact of modifications on the function of BMP protein. The three-dimensional (3D) structure analysis was performed on the nsSNP Y316S, V386G, E387G, C389G, and C391G nsSNP in the TGF- β domain of chicken BMP2 and H344P, S347P, V357A nsSNP in the TGF- β domain of chicken BMP4 protein that was anticipated to be harmful and of high risk. The ability of the proteins to perform variety of tasks interact with other molecules depends on their tertiary structural composition. The current analysis revealed the four most damaging variants (Y316S, V386G, E387G, C389G, and C391G), highly conserved and functional and are located in the TGF-beta domain of BMP2 and BMP4. The amino acid substitutions E387G, C389G, and C391G are discovered in the binding region. It was observed that the mutations in the TGF-beta domain caused significant changes in its structural organization including the substrate binding sites. Current findings will assist future research focused on the role of these variants in BMP function loss and their role in skeletal disorders, and this will possibly help to develop practical strategies for treating bone-related conditions.
Competing Interests: There is no conflict of interest in the conduction of this study.
(Copyright © 2022 Hafiz Ishfaq Ahmad et al.)

Retraction in: Biomed Res Int. 2024 Jan 9;2024:9891352. (PMID: 38230097)

Nucleic Acids Res. 2013 Jan;41(Database issue):D1096-103. (PMID: 23087378)
Bioinformatics. 2008 Oct 15;24(20):2397-8. (PMID: 18757876)
Bone Res. 2016 Apr 26;4:16009. (PMID: 27563484)
Bioinformatics. 2015 Aug 15;31(16):2745-7. (PMID: 25851949)
Stem Cell Res Ther. 2018 Sep 26;9(1):244. (PMID: 30257716)
J Theor Biol. 2008 May 7;252(1):145-54. (PMID: 18342336)
Syst Biol Reprod Med. 2017 Aug;63(4):248-258. (PMID: 28388287)
J Dev Biol. 2021 Jun 28;9(3):. (PMID: 34203252)
J Biomater Sci Polym Ed. 2000;11(8):891-901. (PMID: 11211099)
Nat Protoc. 2016 Jan;11(1):1-9. (PMID: 26633127)
Biomed Res Int. 2021 May 10;2021:5574789. (PMID: 34046497)
Arch Oral Biol. 2019 Jul;103:40-46. (PMID: 31128441)
J Proteome Res. 2011 Dec 2;10(12):5275-84. (PMID: 22050367)
Nat Protoc. 2015 Jun;10(6):845-58. (PMID: 25950237)
Aging (Albany NY). 2020 Feb 11;12(4):3516-3557. (PMID: 32045365)
Genome Biol. 2014 Jan 13;15(1):R19. (PMID: 24451234)
PLoS One. 2017 Mar 15;12(3):e0171355. (PMID: 28296894)
Poult Sci. 2000 Jul;79(7):982-4. (PMID: 10901198)
Bone Rep. 2019 May 05;10:100207. (PMID: 31193008)
J Cell Commun Signal. 2022 Mar;16(1):47-61. (PMID: 34236594)
Nucleic Acids Res. 2017 Jul 3;45(W1):W247-W252. (PMID: 28482034)
Crit Rev Eukaryot Gene Expr. 2019;29(6):551-564. (PMID: 32422010)
Mol Biol Cell. 2005 Oct;16(10):4623-35. (PMID: 16079181)
Arch Biochem Biophys. 2014 Nov 1;561:64-73. (PMID: 25043976)
Methods Mol Biol. 2019;1891:235-245. (PMID: 30414137)
J Mol Biol. 2001 Mar 16;307(1):447-63. (PMID: 11243830)
BMC Bioinformatics. 2010 Nov 08;11:548. (PMID: 21059217)
Dev Dyn. 2022 Jan;251(1):164-177. (PMID: 34133058)
Syst Biol Reprod Med. 2020 Jun;66(3):185-201. (PMID: 31957496)
Bioinformatics. 2013 Oct 15;29(20):2588-95. (PMID: 23975762)
Nat Rev Endocrinol. 2016 Apr;12(4):203-21. (PMID: 26893264)
J Cell Biochem. 2016 Sep;117(9):2023-35. (PMID: 26813965)
Bone. 2020 Aug;137:115368. (PMID: 32380258)
Hum Mutat. 2009 May;30(5):703-14. (PMID: 19267389)
Poult Sci. 2020 Apr;99(4):1946-1955. (PMID: 32241475)
Microb Pathog. 2021 Mar;152:104754. (PMID: 33508415)
PLoS One. 2012;7(10):e46688. (PMID: 23056405)
Bioinformatics. 2006 Nov 15;22(22):2729-34. (PMID: 16895930)
Vet J. 2013 Jun;196(3):477-82. (PMID: 23317659)
Nucleic Acids Res. 2015 Jul 1;43(W1):W174-81. (PMID: 25883148)
J Mol Biol. 2019 May 17;431(11):2197-2212. (PMID: 30995449)
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W252-8. (PMID: 24782522)
Dev Cell. 2009 Mar;16(3):329-43. (PMID: 19289080)
Nat Methods. 2010 Apr;7(4):248-9. (PMID: 20354512)
Cells. 2019 Aug 24;8(9):. (PMID: 31450621)
Microb Pathog. 2020 Oct;147:104361. (PMID: 32622926)
J Biomol NMR. 2015 Sep;63(1):77-83. (PMID: 26195077)
Genes Dis. 2014 Sep;1(1):87-105. (PMID: 25401122)
Hum Mutat. 2009 Mar;30(3):379-90. (PMID: 19085907)
Front Genet. 2021 Feb 04;12:634615. (PMID: 33613647)
Biotechnology (N Y). 1990 Apr;8(4):308-17. (PMID: 1369261)
PLoS Biol. 2004 Nov;2(11):e355. (PMID: 15492776)
Bioinformatics. 2003 Jan;19(1):163-4. (PMID: 12499312)
Protein Sci. 2014 Aug;23(8):1077-93. (PMID: 24888500)
Curr Protoc Hum Genet. 2013 Jan;Chapter 7:Unit7.20. (PMID: 23315928)
PLoS One. 2012;7(10):e43939. (PMID: 23056176)
Res Vet Sci. 2021 Mar;135:569-579. (PMID: 33066991)

0 (Bone Morphogenetic Proteins)
0 (Transforming Growth Factor beta)

Date Created: 20220714 Date Completed: 20220715 Latest Revision: 20240117

20240117

PMC9273450

10.1155/2022/4013729

35832847