Structural Biology UNITCIC bioGUNEBilbao, Spain
Lucy Malinina
Protein-based Structural Biomedicine
is a part of STRUCTURAL BIOLOGY
aimed at using structural knowledge to
control and pharmacologically modulate
protein properties
is a part of STRUCTURAL BIOLOGY
aimed at using structural knowledge to
control and pharmacologically modulate
protein properties
Manipulating Protein SpecificityManipulating Protein Specificity
|||||||||| Protein-RNA specificity |||||||||||||||||||||||||| Protein-RNA specificity ||||||||||||||||
||||||||| Protein-Lipid Selectivity |||||||||||||||||||||||| Protein-Lipid Selectivity |||||||||||||||
PART I. Introduction to STRUCTURAL BIOLOGY
PART II. GLTP, GlycoLipid Transfer Protein
PART III. P19, suppressor of RNAi
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
STRUCTURAL BIOLOGY
makes known the structure of biomolecules
• structure determination• structure analysis:
i) description ii) relationship to
function iii) generalizations
• structure determination• structure analysis:
i) description ii) relationship to
function iii) generalizations
Basic techniques of STRUCTURAL BIOLOGY
•Macromolecular X-ray Crystallography
•Electron Microscopy - EM
•Nuclear Magnetic Resonance - NMR
Useful for very large assemblies, where X-ray crystallography becomes very difficult
Molecules, complexes, assemblies - as single crystals
Molecules in solution; useful to study flexible parts, invisible for X-ray crystallography
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
CRYSTALIZATION
X-RAY DATA COLLECTION
“SOLVING” THE STRUCTURE
DNA double helix: A, B, Z
Stem-loop RNA structure, hairpin
RNA molecules are not double helices, neighter single strands. RNAs are “highly structured”.
PROTEINS
-Helix
-Structure
Turns
Loops
are often flexible
and therefore disordered in crystals
Viral suppressor of RNAi p19
FOLDS
DOMAINS
MOTIVES
OB-fold
N
C
β1
β2
β3
β4
β5
α34 L12
L45
RPA32 core(OB-D)
RPA14
Structural conservation between
RPA70OB-B / ssDNA
W361
F386
5’
3’
300
420
L45