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Protein Folding of
A Biopharmaceutical — hCD83
Lin Zhang
Chemical Engineering
Department
Biopharmaceuticals
Proteins
In use:
Insulin
Potential use:
tPA
Human CD83
Outlines

Backgrounds of hCD83

Preliminary Results and Discussion
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
Backgrounds
hCD83
Argos
DC Bio
Preclinical Trial
Production
Backgrounds
Insulin
Backgrounds
What we are interested in:



Dynamic process of protein folding
Protein Aggregation
3D Structure
Backgrounds
FDA Approval
3D Structure
Crystallography
3D Structure Prediction Flowchart
Target Sequence
Conserved Domain
Ⅰ
Yes
No
Homologous
in PDB
Secondary
Structure
Comparative
Modeling
Comparison
Tertiary
Structure
Ⅱ
Preliminary Results
Descriptions
Database Searching
Protein-Protein Blast
Preliminary Results
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
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)

Superfamily: Immunoglobulin
(IG)

Family: V set domains
(antibody variable domain-like)

Family: I set domains
Preliminary Results
Protein fold recognition
1nez_g
Phyre
Preliminary Results
Ⅰ Comparative Modeling
Swiss-Model
RAPTOR
Preliminary Results
Swiss-Model
1MCP_H
(7~121)
Preliminary Results
Swiss-Model
1a6w_L
Discussion
Common
Discussion
Differences
1MCP_H
1α-helix
e
f
Discussion
Differences
1a6w_L
b
c
e
f
2α-helices
Preliminary Results
RAPTOR
1a49_a
Preliminary Results
1a49_a
1 α-helix:
e
f : Thr(83)~Ser(87)
Preliminary Results
Ⅱ Secondary Structure and Tertiary Structure
Secondary Structure: PHD and Jnet
Tertiary Structure :
HMMSTR
Preliminary Results
PHD
Preliminary Results
Jnet
Discussion
Secondary Structure
PHD: 6 β-strands, no α-helix, not to be globular protein
V(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-helix
V(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)
Preliminary Results
HMMSTR
Discussion
HMMSTR
3 α- helices:
Asp(98)~Asn(102)
Pro(115)~Arg (118)
Lys(119)~Ile(130)
Discussion
Comparison
A. Fold Pattern
Comparative Modeling: distinguished hydrophobic
core and hydrophilic side,
regular, tight
HMMSTR: irregular, loose pattern, no related motif
Discussion
Comparison
B. Composition
Comparative Modeling: more beta-strands and loops
as well as hydrogen bonds
HMMSTR: less beta-strands, loops and hydrogen bonds