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About

The focus of our lab is to understand the structural basis of assembly and function of various heterochromatin-associated multiprotein complexes.

We primarily use electron cryo-microscopy to investigate these complexes which is complemented by biochemical, biophysical characterization and in vitro and in vivo functional assays.

The major questions we tackle are:
– How are these multiprotein complexes assembled?
– How do these complexes lead to heterochromatin formation?
– How do these complexes regulate heterochromatin?
– How are these complexes involved in DNA repair of heterochromatin region?
– Is there a crosstalk between several of these complexes?

Publications

Selected publications from A/Prof Shabih Shakeel

Sijacki T, Alcón P, Chen ZA, McLaughlin SH, Shakeel S, Rappsilber J, Passmore LA. The DNA-damage kinase ATR activates the FANCD2-FANCI clamp by priming it for ubiquitination. Nature Structural & Molecular Biology. 2022;29(9):10.1038/s41594-022-00820-9

Alcón P, Shakeel S, Chen ZA, Rappsilber J, Patel KJ, Passmore LA. FANCD2–FANCI is a clamp stabilized on DNA by monoubiquitination of FANCD2 during DNA repair. Nature Structural & Molecular Biology. 2020;27(3):10.1038/s41594-020-0380-1

Shakeel S, Rajendra E, Alcón P, O’Reilly F, Chorev DS, Maslen S, Degliesposti G, Russo CJ, He S, Hill CH, Skehel JM, Scheres SHW, Patel KJ, Rappsilber J, Robinson CV, Passmore LA. Structure of the Fanconi anaemia monoubiquitin ligase complex. Nature. 2019;575(7781):10.1038/s41586-019-1703-4

Shakeel S, Dykeman EC, White SJ, Ora A, Cockburn JJB, Butcher SJ, Stockley PG, Twarock R. Genomic RNA folding mediates assembly of human parechovirus. Nature Communications. 2017;8(1):10.1038/s41467-016-0011-z

Shakeel S, Westerhuis BM, Domanska A, Koning RI, Matadeen R, Koster AJ, Bakker AQ, Beaumont T, Wolthers KC, Butcher SJ. Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis. Nature Communications. 2016;7(1):10.1038/ncomms11387

Shakeel S, Westerhuis BM, Ora A, Koen G, Bakker AQ, Claassen Y, Wagner K, Beaumont T, Wolthers KC, Butcher SJ. Structural Basis of Human Parechovirus Neutralization by Human Monoclonal Antibodies. Journal of Virology. 2015;89(18):10.1128/jvi.01429-15

Shakeel S, Seitsonen JJT, Kajander T, Laurinmäki P, Hyypiä T, Susi P, Butcher SJ. Structural and Functional Analysis of Coxsackievirus A9 Integrin αvβ6 Binding and Uncoating. Journal of Virology. 2013;87(7):10.1128/jvi.02989-12

Tan W, Leis A, Venugopal H, Shakeel S. Mechanism of autoinhibition and activation of the human MORC2 GHKL ATPase. Acta Crystallographica Section A: Foundations and advances. 2023;79(a2):10.1107/s2053273323087545

Laurinmäki P, Shakeel S, Ekström J-O, Mohammadi P, Hultmark D, Butcher SJ. Structure of Nora virus at 2.7 Å resolution and implications for receptor binding, capsid stability and taxonomy. Scientific Reports. 2020;10(1):10.1038/s41598-020-76613-1

Farrell DP, Anishchenko I, Shakeel S, Lauko A, Passmore LA, Baker D, DiMaio F. Deep learning enables the atomic structure determination of the Fanconi Anemia core complex from cryoEM. IUCrJ. 2020;7(Pt 5):10.1107/s2052252520009306

Casañal A, Shakeel S, Passmore LA. Interpretation of medium resolution cryoEM maps of multi-protein complexes. Current Opinion in Structural Biology. 2019;58:10.1016/j.sbi.2019.06.009

Shakeel S, Evans JD, Hazelbaker M, Kao CC, Vaughan RC, Butcher SJ. Intrinsically-disordered N-termini in human parechovirus 1 capsid proteins bind encapsidated RNA. Scientific Reports. 2018;8(1):10.1038/s41598-018-23552-7

Karelehto E, van der Sanden S, Geraets JA, Domanska A, van der Linden L, Hoogendoorn D, Koen G, van Eijk H, Shakeel S, Beaumont T, de Jong M, Pajkrt D, Butcher SJ, Wolthers KC. Strain-dependent neutralization reveals antigenic variation of human parechovirus 3. Scientific Reports. 2017;7(1):10.1038/s41598-017-12458-5

Shakeel S, Dykeman EC, White SJ, Ora A, Cockburn JJB, Butcher SJ, Stockley PG, Twarock R. Erratum: Genomic RNA folding mediates assembly of human parechovirus. Nature Communications. 2017;8(1):10.1038/s41467-017-00026-4

Pandurangan AP, Shakeel S, Butcher SJ, Topf M. Combined approaches to flexible fitting and assessment in virus capsids undergoing conformational change. Journal of Structural Biology. 2014;185(3):10.1016/j.jsb.2013.12.003

Seitsonen JJT, Shakeel S, Susi P, Pandurangan AP, Sinkovits RS, Hyvönen H, Laurinmäki P, Ylä-Pelto J, Topf M, Hyypiä T, Butcher SJ. Structural Analysis of Coxsackievirus A7 Reveals Conformational Changes Associated with Uncoating. Journal of Virology. 2012;86(13):10.1128/jvi.06425-11

Shakeel S, Karim S, Ali A. Peptide Nucleic Acids (PNAs). ChemInform. 2007;38(7):10.1002/chin.200707246

Lab research projects

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