Solution Structure of the Methyl-CpG Binding Domain of Human MBD1 in Complex with Methylated DNA

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I. Introduction

MBD1 protein

DNA methylation is an important factor in control of gene expression in organisms. Increased DNA methylation is associated with gene silencing.  Improper methylation can induce many damaging genetic defects in organisms.  Increased methylation of tumor suppressor genes (which inhibits their transcription) or decreased methylation of genes that promote cell growth (possible protooncogenes) have been carcinogenesis.  Methylation of DNA is catalyzed by DNA methyltransferases.  The structure here is the methyl-CpG binding domains (MBDs) of human methylated DNA Binding Protein 1 (MDB1) bound to methylated DNA.   .   

For more information see Biochemistry Online: Chapter 5D - Binding and the Control of Gene Transcription

II. General Structure

Methylated DNA and MDB1 protein (methyl group in yellow)
MDB1 protein Backbone
Major/Minor Grooves with methyl groups
Backbone and sidechains of MDB1 protein
Cartoon, Hbonds and Wireframe
Active site residues (Val 20, Arg 22, Tyr 34, Arg 44, Ser 45) MDB1 is able to bind to methylated DNA through the use of 5 highly conserved side chains.
Methylated DNA (methyl groups in yellow) and MDB1 active site residues (Val 20, Arg 22, Tyr 34, Arg 44, Ser 45)
Loop L1 (residues 22-30)  This loop undergoes a conformational change to allow it to bind to the major groove of DNA.
Methylated DNA and binding site of MDB1 (Loop L1)
Methylated DNA with binding MDB1 and active site.  The L1 loop binds to DNA and the active site is then able to interact with the methyl groups present.