Structural Basis for Multi-specificity of MRG Domains

Abstract

Summary Chromatin-binding proteins play vital roles in the assembly and recruitment of multi-subunit complexes harboring effector proteins to specific genomic loci. MRG15, a chromodomain-containing chromatin-binding protein, recruits diverse chromatin-associated complexes that regulate gene transcription, DNA repair, and RNA splicing. Previous studies with Pf1, another chromatin-binding subunit of the Sin3S/Rpd3S histone deacetylase complex, defined the sequence and structural requirements for interactions with the MRG15 MRG domain, a common target of diverse subunits in the aforementioned complexes. We now show that MRGBP, a member of the Tip60/NuA4 histone acetyltransferase complex, engages the same two surfaces of the MRG domain as Pf1. High-affinity interactions occur via a bipartite structural motif including an FxLP sequence motif. MRGBP shares little sequence and structural similarity with Pf1, yet, targets similar pockets on the surface of the MRG domain, mimicking Pf1 in its interactions. Our studies shed light into how MRG domains have evolved to bind diverse targets.

Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila

“…Mrg15 (also known as Eaf3 in yeast) contains an N-terminal chromo domain that has been reported to recognize H3K36me2/3, although the binding affinities of Mrg15 for methylated H3K36me2/3 peptides are fairly low ( K d ≈ 200–400 μM) 31 – 33 . Mrg15 also contains a C-terminal MRG domain that is mainly responsible for protein–protein interactions 34 – 37 . Mrg15 and the yeast homolog Eaf3 have been reported to be subunits of two other histone-modifying enzyme complexes: the NuA4 histone acetyltransferase complex 38 – 41 and the Rpd3S (or Sin3a in higher eukaryotes) histone deacetylase complex 42 – 46 .…”

Structural studies on MRG701 chromodomain reveal a novel dimerization interface of MRG proteins in green plants

“…The MRG domains form homodimers and interact with other proteins to form functional complexes (Zhang et al, 2006b; Xie et al, 2015). As a “Royal Family” member, the N-terminal chromodomain functions as a histone reader that specifically recognizes methylated histone markers (Yap and Zhou, 2011).…”

The influence of intrinsic folding mechanism of an unfolded protein on the coupled folding‐binding process during target recognition

“…The coupled folding‐binding process is a complex process. The binding target could dictate the folded structure and the folding mechanism of IDPs, which is reflected in binding of different IDPs to a common target and an IDP to different targets . Very recently, N TAIL /XD and N TAIL /hsp70 interactions were comparatively investigated.…”

“…The binding target could dictate the folded structure and the folding mechanism of IDPs, which is reflected in binding of different IDPs to a common target and an IDP to different targets. [63][64][65][66] Very recently, N TAIL /XD and N TAIL /hsp70 interactions were comparatively investigated. It was found that N TAIL adopts different conformations upon binding to XD and hsp70, and the binding mechanisms are different.…”