Solution NMR backbone assignments of disordered Olduvai protein domain CON1 employing Hα-detected experiments

被引:0
作者
Natasia Paukovich
Morkos A. Henen
Alya Hussain
Aaron Issaian
James M. Sikela
Kirk C. Hansen
Beat Vögeli
机构
[1] University of Colorado,Department of Biochemistry & Molecular Genetics, School of Medicine
[2] Mansoura University,Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy
来源
Biomolecular NMR Assignments | 2022年 / 16卷
关键词
Olduvai domain; DUF1220; IDP; Autism; Backbone chemical shift assignment;
D O I
暂无
中图分类号
学科分类号
摘要
Olduvai protein domains, encoded by the NBPF gene family, are responsible for the largest increase in copy number of any protein-coding region in the human genome. This has spawned various genetics studies which have linked these domains to human brain development and divergence from our primate ancestors, as well as currently relevant cognitive diseases such as schizophrenia and autism spectrum disorder (ASD). There are six separate Olduvai domains which together form the majority of the various protein products of the NBPF genes. The six domains include three conserved domains (CON1-3), and three human-lineage-specific domains (HLS1-3) which occur in triplet. Here, we present the solution nuclear magnetic resonance backbone assignments for the CON1 domain, which has been linked to the severity of ASD. The data confirm that CON1 is an intrinsically disordered protein (IDP). Additionally, we use innovative Hα-detected experiments which allow us to not only assign the Hα atoms and N atoms of proline residues, but also to assign residues where HN-experiments suffered from peak overlap or broadening.
引用
收藏
页码:113 / 119
页数:6
相关论文
共 100 条
[1]  
Adamski W(2019)A unified description of intrinsically disordered protein dynamics under physiological conditions using NMR spectroscopy J Am Chem Soc 141 17817-17829
[2]  
Salvi N(2018)Propensity for cis-proline formation in unfolded proteins ChemBioChem 176 643-650
[3]  
Maurin D(2007)Protein NMR Spectroscopy In Protein NMR Spectroscopy 6 277-293
[4]  
Magnat J(2019)A third linear association between Olduvai (DUF1220) copy number and severity of the classic symptoms of inherited autism Am J Psychiatry 52 315-327
[5]  
Milles S(1995)NMRPipe: a multidimensional spectral processing system based on UNIX pipes J Biomol NMR 29 4659-4667
[6]  
Jensen MR(2012)Application of iterative soft thresholding for fast reconstruction of NMR data non-uniformly sampled with multidimensional Poisson Gap scheduling J Biomol NMR 13 339-343
[7]  
Abyzov A(1990)A novel approach for sequential assignment of 1H, 13C, and 15N spectra of larger proteins: heteronuclear triple-resonance three-dimensional NMR spectroscopy application to calmodulin Biochemistry 74 741-752
[8]  
Moreau CJ(2019)Solution NMR backbone assignment reveals interaction-free tumbling of human lineage-specific Olduvai protein domains Biomol NMR Assign 31 1325-1327
[9]  
Blackledge M(2002)HACANCOi: a new Hα-detected experiment for backbone resonance assignment of intrinsically disordered proteins Insights into the Structure and Dynamics of Unfolded Proteins from Nuclear Magnetic Resonance 49 99-109
[10]  
Alderson TR(2020)NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy J Biomol NMR 15 2795-696