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?


Selected publications from A/Prof Shabih Shakeel

1. Shakeel S, Rajendra E, Alcón P, O’Reilly F, Chorev DS, Maslen S, Degliesposti G, Russo CJ, He S, Hill CH et al. Structure of the Fanconi anaemia monoubiquitin ligase complex. Nature. 2019. 575, 234-237 PMID: 31666700

2. 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. Nat Struct Mol Biol. 2020. 27, 240-248 PMID: 32066963

3. 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. Nat Struct Mol Biol. 2022. 29,881-890. PMID: 36050501

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. Nat Comm. 2017. 8, PMID: 28232749

5. 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. Nat Comm. 2016. 7, 11387 PMID: 27435188

6. 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, 881-892 PMID: 32939280

7. 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. J Virol. 2015. 89, 9571-9580 PMID: 26157123

8. Pandurangan AP, Shakeel S, Butcher S, Topf M. Combined approaches to flexible fitting and assessment in virus capsids undergoing conformational change. J Struct Biol. 2014. 185, 427-439 PMID: 24333899

9. Shakeel S, Seitsonen JJ, Kajander T, Laurinmaki P, Hyypiä T, Susi P, Butcher SJ. Structural and functional analysis of coxsackievirus A9 integrin alphavbeta6 binding and uncoating. J Virol. 2013. 87, 3943-3951 PMID: 23365426

10. Seitsonen JJ, Shakeel S, Susi P, Pandurangan AP, Sinkovits RS, Hyvonen H, Laurinmaki P, Yla-Pelto J, Topf M, Hyypiä T et al. Structural analysis of coxsackievirus A7 reveals conformational changes associated with uncoating. J Virol. 2012. 86, 7207-7215 PMID: 22514349

Lab research projects

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