Solution Structure and Molecular Interactions of Lamin B Receptor Tudor Domain

Abstract

Background: Lamin B receptor (LBR) is an integral nuclear envelope protein and contains a Tudor domain. Results:The NMR structure of LBR-Tudor was determined and its interactions with nuclear proteins, histones, and nucleosomes were explored. Conclusion: LBR-Tudor is not involved in recognition of methylated histones and binds free H3. Significance: Tudor domains may act as histone chaperone-like platforms.

Lamin B Receptor Recognizes Specific Modifications of Histone H4 in Heterochromatin Formation

“…In contrast, a tudor domain-deletion mutant, LBR ⌬1-53 , and the mutants in which aromatic residues were substituted with alanine, LBR W16A and LBR Y23A , moved ϳ7 times faster than the LBR WT (diffusion coefficients were 0.230 Ϯ 0.007, 0.253 Ϯ 0.007, and 0.267 Ϯ 0.006 m 2 /s, respectively). A similar result showing increased mobility of a tudor domain-deletion LBR mutant by FRAP analysis was also reported previously (15,33). Further experiments showed that alanine substitutions of tyrosine 41 and aspartic acid 43 in the histone code-reading pocket of the tudor domain (Fig.…”

“…A previous report showed that the LBR tudor domain binds to histone H3 but not to H4. However, the study also demonstrated that the RS domain of LBR can bind to histone H4 in vitro (15). We argue that the tudor domain is essential for recognition of the H4 modifications because NP W16A lacks histone modification binding specificity.…”

“…Thus, LBR may also recognize some specific histone modifications. However, recent studies show that the tudor domain of LBR does not appear to bind methylated lysine or arginine residues (15). They show that not only the tudor domain but also the RS domain binds to histone and that the binding of LBR to chromatin is affected by the globular II domain in vivo (20) (for the domain structures of LBR, see Fig.…”

“…It has been reported that LBR binds to histones and DNA via its tudor domain (amino acid residues 1-62) and RS domain (amino acid residues 53-89), respectively (11,15). Tudor domains are methylation-specific "histone code-reading" domains, as are chromo, MBT (malignant brain tumor) and WD-repeat domains (16 -18).…”

ELYS regulates the localization of LBR by modulating its phosphorylation state

“…The N-terminal region of LBR comprises a Tudor domain (also called the globular I domain) and a globular II domain, which are linked by a hinge region (Liokatis et al, 2012; Ye et al, 1997). The hinge region contains a nuclear localization signal (NLS), which is required for the interaction with importin β (Ma et al, 2007), and an arginine-serine repeat (RS) domain, which consists of multiple repeats of arginine and serine residues (Sellis et al, 2012).…”