Structural Biology

Overview

Experimental Approaches

  Research Areas

Equipment and Experimental Facilities

Structural Biology Faculty 


Structural Biology encompasses all of those who determine the 3D structures of proteins and nucleic acids by a variety of methods including NMR spectroscopy, x-ray crystallography, electron microscopy, EPR spectroscopy, and atomic force microscopy. The Program offers advanced courses in both x-ray crystallography (BIOP802) and NMR spectroscopy (BIOP803) to facilitate training in these areas.

Structural Biology Approaches at UVa  
A detailed understanding of biological function requires detailed structures of the macromolecules that comprise the machinery of life. These structures provide uniquely insights into the molecular basis of function and provide a rational framework for the design of experiments to address the biological function of a macromolecule. In addition, structures of medically relevant targets play a critical role in accelerating the process of drug design through the use of structure-based lead discovery.

Structural biology spans many different methodologies that provide unique and complementary information about the structure of macromolecules. The major experimental methods for moderate to high-resolution macromolecular structure determination are x-ray crystallography (Bauerle , Bushweller, Derewenda, Khorasanizadeh, Kretsinger, Minor, Rastinejad, Wiener) and solution nuclear magnetic resonance (NMR) spectroscopy (Bryant, Bushweller, Khorasanizadeh, Tamm).  Both structural and dynamic information can be gleaned from EPR spectroscopy (Cafiso, Perozo) in many systems where x-ray and NMR approaches cannot be applied. For studies of higher-order structures of large macromolecular complexes, both electron microscopy (Egelman) and atomic force microscopy (Shao ) are powerful tools. All of the structural biology laboratories at UVA combine a core of one or more structural methods with other experimental approaches to pursue the molecular basis of biological function.  Many of the structural biology faculty are also intimately involved in methodology development for various of these technologies.

Structural Biology Research Areas at UVa : 

Structural biology at UVa focuses on numerous important biological areas including:

 

 

 

Rho

 

Signal transduction
Projects include Rho-GTPase and its associated proteins, ERM (ezrin-radixin-moesin), proteins involved in neuronal migration, and nuclear receptors ( Cafiso, Derewenda, Rastinejad ).

DCX domain structure, collaborative project between the Derewenda and Bushweller labs (Nat. Struc. Mol. Biol. 10, 324-333 (2003)).

DNA/RNA-protein interactions and transcription factors
Projects include core-binding factor, chromatin-modifying enzymes, and nuclear receptors (Bushweller, Egelman,Khorasanizadeh , Rastinejad , Shao).

structure3 Electron density for the structure of the HHR domain of AML1-ETO, a collaborative project between the Bushweller and Minor labs.

 

 

 

Macromolecular assemblies
Projects include the RecA filament, actin, and herpes virus capsid (Egelman, Shao ).

Hexamer ring structure of RuvB on dsDNA, project in the Egelman lab (J. Mol. Biol. 321, 839-849 (2002)).

 

RecA

 

membrane Membrane proteins
Projects include ion channels, transporters and membrane-bound enzymes (Bushweller , Cafiso,Perozo, Tamm, Wiener ).

Structure of the integral membrane protein BtuB, a project in the Wiener lab (Nat. Struc. Mol. Biol. 10, 394-401 (2003))

 

Methodology development
Projects include rational surface mutagenesis for crystallization, membrane protein crystallization, data reduction & analysis software, scanning force microscopy technology development (Derewenda,Minor, Shao, Wiener). Members of this group are participants in several prestigious Structural Genomics Centers (Derewenda, Minor, Wiener ) whose goal is the development of approaches for the high-throughput determination of protein 3D structures.

Structural Biology Equipment at UVa 

Structural biology experimental facilities utilized by research groups here at UVa include:

NMR spectrometers - two 600 MHz spectrometers equipped for 4 channel operation with one 600 equipped with a cryoprobe,   two 500 MHz spectrometers equipped for 4 channel operation, one 360 MHz sprectrometer, and a 300 MHz machine equipped with high power probes for solids.

X-ray crystallography - three rotating-anode x-ray generators with multiple detectors (image plate and CCD), multilayer x-ray optics, cryosystems.

Electron & scanning probe microscopy - Two field-emission gun electron microscopes and several AFMs, including a unique instrument that operates at cryogenic temperatures and that was developed at UVa.  

For a list of faculty currently conducting research in this area,  click here.