Structural Biology of RNA-Binding Domains

RNA binding proteins are involved in every step of RNA metabolism. Most of them consist of small RNA-binding domains that are required for their recruitment to specific RNA targets. The interaction between proteins and RNA affects the structure of RNA and plays a key role in its biogenesis, stability, function, transport and cellular localization. Usually full-length phase isolated proteins do not have a well-defined structure due to their large size, high degree of disorder, and ease of aggregation. In contrast, the structures of RNA-binding domains provide important insights into the protein-nucleic acid interactions behind liquid-liquid phase separation (LLPS). Human proteomics studies have shown that RNA binding proteins are associated with cell cycle checkpoint defects, genomic instability and cancer. Thus, a comprehensive, mechanistic understanding of various cellular processes requires the identification of RNA binding proteins and RNA binding sites.

Fig. 1. Structures of zinc finger, KH domain and dsRBM in complex with RNA. (Cléry A, et al., 2012)

Customized Services

RNA binding proteins have multiple functions within the cell, but the number of annotated RNA binding proteins is relatively small. We are committed to analyzing RNA binding proteins and RNA interactions through structure determination techniques and computational modeling. CD BioSciences integrates structural data currently available for protein-RNA complexes and develops advanced methods to resolve the three-dimensional structure of RNA binding proteins at atomic resolution.

• X-Ray crystallography.
• Solution nuclear magnetic resonance (NMR).
• Cryo-electron microscopy (cryo-EM).

In addition, we provide computational methods to predict interactions in RNA-binding proteins and to model the docking and dynamics of bound structures. Our computational approach focuses on three key areas:

(1) Predicting RNA Binding Sites on RNA-Binding Protein Structures

Based on the physical and/or chemical parameters of RNA-binding residues obtained by experimental methods, we use this information to search for similar sites on target proteins. Common sequence features used are the position-specific scoring matrix and amino acid propensity, which quantify the propensity of amino acids to binding sites. Common structural features include the solvent accessibility of amino acids, surface electrostatic potential and geometric properties such as shape.

To our customers' satisfaction, we offer prediction techniques using these features, including machine learning (ML), template methods, and scoring methods to predict the position of RNA binding sites on the structure of RNA binding proteins.

(2) Docking of RNA to RNA-Binding Proteins

We have multiple methods for docking proteins to RNA and offer customized processes.

(a) Structural docking.

(b) Scoring of the resulting complexes using potentials based on known chemical and/or structural properties of the complexes

(c) Selection of the "best" model based on the core.

(d) Model refinement.

(e) Molecular dynamics of simulated protein-RNA interactions.

(3) Molecular Dynamics Simulation of Protein-RNA Interaction

Our team of experts is committed to developing protein-RNA specific software for MD simulations as well as more complex RNA specific force fields to simulate the molecular dynamics of protein-RNA complexes.

Most RNA-binding proteins contain several structural domains, including different types of RNA-binding motifs, which specifically recognize RNA sequences. Our structural biologists focus on analyzing the structure of these RNA-binding domains, containing:

• RNA Recognition Motifs (RRM)
• Zinc Finger Structural Domains
• KH Structural Domains
• Double-Stranded RNA Binding Motifs (dsRBM)

Why Choose Us

• Cutting-edge protein-RNA complex assays.
• Molecules are visible at higher resolution (<2.5 Å).
• Experimentally generated structure collections can give dynamic images of RNA-binding proteins.
• A wealth of structural biology data supports protein-RNA interactions.

We provide detailed structural data to help you better understand RNA-binding protein function and protein-RNA interactions in the RNA-binding domain. If you are interested in our services, please do not hesitate to contact us for more information.