Structural Biology UNIT CIC bioGUNE Bilbao, Spain

Protein-based Structural Biomedicine Lucy Malinina lucy@cicbiogune.es Structural Biology UNIT CIC bioGUNE Bilbao, Spain

Protein-based Structural Biomedicine is a part of STRUCTURAL BIOLOGY aimed at using structural knowledge to control and pharmacologically modulate protein properties

Manipulating Protein Specificity  ||||||||| Protein-Lipid Selectivity ||||||||||||||| ||||||||||Protein-RNA specificity ||||||||||||||||

PART I.Introduction to STRUCTURAL BIOLOGY PART II.GLTP,GlycoLipid Transfer Protein PART III.P19,suppressor of RNAi

STRUCTURAL BIOLOGY makes known the structure of biomolecules • structure determination • structure analysis: i) description ii) relationship to function iii) generalizations

Basic techniques of STRUCTURAL BIOLOGY Molecules, complexes, assemblies - as single crystals • Macromolecular X-ray Crystallography • Electron Microscopy - EM • Nuclear Magnetic Resonance - NMR Useful for very large assemblies, where X-ray crystallography becomes very difficult Molecules in solution; useful to study flexible parts, invisible for X-ray crystallography

CRYSTALIZATION X-RAY DATA COLLECTION “SOLVING” THE STRUCTURE With X-rays, we can detect diffraction from molecules, but we then have to apply some experimental tricks to solve a phase problem and use a computer to reassemble the image. This is the essence of the X-ray macromolecular crystallography

DNA double helix: A, B, Z

Stem-loop RNA structure, hairpin

RNA molecules are not double helices, neighter single strands. RNAs are “highly structured”. Ribozyme

PROTEINS

-Helix

-Structure

Turns

Loops are often flexible and therefore disordered in crystals

Viral suppressor of RNAi p19

FOLDS DOMAINS MOTIVES

β5 C L45 β4 β1 N L12 α34 β2 β3 OB-fold

Structural conservation between RPA70 OB-B / ssDNA RPA32core (OB-D) RPA14 5’ L45 W361 3’ F386 300 420

Structural Biology UNIT CIC bioGUNE Bilbao, Spain