protein folding of a biopharmaceutical — hcd83 lin zhang chemical engineering department
TRANSCRIPT
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Protein Folding of A Biopharmaceutical — hCD83
Lin Zhang
Chemical Engineering
Department
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Biopharmaceuticals
Proteins
In use: Insulin tPA
Potential use: Human CD83
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Outlines
Backgrounds of hCD83
Preliminary Results and Discussion
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Human CD83 (hCD83)
Human CD83 is expressed predominantly on the surface of dendritic cells (DCs)
DCs are the most potent antigen presenting cells of the immune system
Glycoprotein CD83 is one of the best-known maturation markers for human DCs
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Backgrounds
hCD83
ArgosDC Bio
Production
Preclinical Trial
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Backgrounds
Insulin
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Backgrounds
What we are interested in:
Dynamic process of protein folding Protein Aggregation 3D Structure
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Backgrounds
FDA Approval
3D Structure
Crystallography
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3D Structure Prediction Flowchart
Target Sequence
Homologous in PDB
Secondary Structure
Comparative Modeling
Tertiary Structure
Conserved Domain
Yes No
ⅡⅠ
Comparison
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Preliminary Results
Database Searching Protein-Protein Blast
Descriptions
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Preliminary Results
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Preliminary Results
1MCP_H
Class: All beta proteins
Fold: Immunoglobulin-like beta-sandwich
sandwich; 7 strands in 2 sheets; greek-key some members of the fold have additional strands
Superfamily: Immunoglobulin (IG)
Family: V set domains (antibody variable domain-like)
1GL4_B
Class: All beta proteins
Fold: Immunoglobulin-like beta-sandwich
sandwich; 7 strands in 2 sheets; greek-key some members of the fold have additional strands
Superfamily: Immunoglobulin (IG)
Family: I set domains
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Preliminary Results
Protein fold recognition Phyre
1nez_g
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Preliminary Results
Ⅰ Comparative Modeling
Swiss-Model
RAPTOR
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Preliminary Results
1MCP_H
(7~121)
Swiss-Model
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Preliminary Results
Swiss-Model
1a6w_L
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Discussion
Common
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Discussion
Differences
1MCP_H
1α-helix e f
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Discussion
Differences
1a6w_L
b c
2α-helices
e f
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Preliminary Results
RAPTOR
1a49_a
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Preliminary Results
1a49_a
1 α-helix: e f : Thr(83)~Ser(87)
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Preliminary Results
Ⅱ Secondary Structure and Tertiary Structure
Secondary Structure: PHD and Jnet
Tertiary Structure : HMMSTR
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Preliminary Results
PHD
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Preliminary Results
Jnet
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Discussion
Secondary Structure
PHD: 6 β-strands, no α-helix, not to be globular proteinV(8)~V(10), D(17)~C(20), V(32)~K(36), S(76)~N(81),
T(89)~L(94), V(107)~T(112)
Jnet: 8 β-strands, no α-helixV(8)~C(12), D(15)~T(21), T(31)~K(36), E(43)~T(47)
N(64)~D(68), Y(75)~N(81), T(89)~Q(95), G(104)~T(112)
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Preliminary Results
HMMSTR
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Discussion
HMMSTR
3 α- helices:
Asp(98)~Asn(102)
Pro(115)~Arg (118)
Lys(119)~Ile(130)
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Discussion
Comparison
A. Fold PatternComparative Modeling: distinguished hydrophobic core and hydrophilic side, regular, tight
HMMSTR: irregular, loose pattern, no related motif
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Discussion
Comparison
B. CompositionComparative Modeling: more beta-strands and loops
as well as hydrogen bonds
HMMSTR: less beta-strands, loops and hydrogen bonds