Cell Biology:

Vesicular Transportation

Dr. Amit Joshi

HOD & Assistant Professor
Biochemistry Department
KALINGA UNIVERSITY
Naya Raipur, CG, INDIA-492101
 COP-I Vesicle Formation

A B
COP-II Vesicle Formation
Clathrin Coat Vesicle Formation
ER: KDEL & KKXX SIGNATURE
SEQUENCE
• The KKXX and KDEL sequences are signal sequences found in proteins that are involved in
the regulation of protein trafficking within the cell, particularly in the context of vesicular
transport between the endoplasmic reticulum (ER) and the Golgi apparatus. These sequences
play a crucial role in targeting and retaining proteins within the ER or in retrieving them from
the Golgi apparatus back to the ER.
KKXX Sequence:
• The KKXX sequence is a retrieval signal found at the C-terminus of some ER-resident
membrane proteins or soluble ER proteins. The most well-known KKXX-containing protein
is the KDEL receptor (These are present on Transmembrane proteins of RER).
• The KKXX sequence functions as a retrieval signal that helps maintain ER-resident proteins
within the ER. It interacts with COPI (Coat Protein I) vesicles, which are involved in
retrograde transport from the Golgi apparatus back to the ER.
• When a protein containing the KKXX signal is transported to the Golgi apparatus, COPI
vesicles recognize the KKXX sequence and transport the protein back to the ER, preventing
its accumulation in the Golgi.
KDEL Sequence:
• The KDEL sequence is a retrieval signal found at the C-terminus of
soluble ER-resident proteins, such as chaperone proteins like BiP
(Binding immunoglobulin Protein).
• Proteins containing the KDEL sequence are typically enzymes or
chaperones that need to be retained within the ER for proper protein
folding and quality control.
• The KDEL sequence interacts with the KDEL receptor, a transmembrane
protein in the Golgi apparatus. When KDEL-containing proteins escape
from the ER and reach the Golgi, they are recognized by the KDEL
receptor.
• The KDEL receptor binds to KDEL-containing proteins and directs them
back to the ER via retrograde transport vesicles, such as COPI-coated
vesicles.
Resident proteins that escape the ER are captured by the KDEL receptor
and retrieved in a COPI dependent process
KKXX Sequence:
• Proteins with the KKXX sequence also have it encoded in their amino acid sequence.
• The COPI complex recognizes the KKXX sequence and, when a protein bearing this
signal reaches the Golgi apparatus, COPI-coated vesicles are formed around it.
• These vesicles transport the protein back to the ER, where they fuse with the ER
membrane, releasing the protein into the ER lumen.
• The protein can then be sorted or folded within the ER or continue on to other destinations
if needed.
KDEL Sequence:
• Proteins that are meant to carry the KDEL sequence usually have it encoded in their amino
acid sequence. This sequence is recognized by the KDEL receptor (ERD2) as the protein
exits the Golgi apparatus.
• The KDEL receptor binds to the KDEL sequence, allowing the protein to be transported
back to the ER via vesicles budding from the Golgi apparatus.
• Once in the ER, the protein is released from the receptor and can continue to perform its
functions within the ER.
• The high resolution of the crystal structures obtained using lipid cubic
phase crystallisation revealed that KDEL binding results in the
formation of a very short hydrogen bond, an extremely rare intra
molecular interaction.

• This bond only forms when the pH of the binding site is acidic and helps
to explain how pH changes between the ER and Golgi help to drive
protein trafficking in one direction. (In Cis Golgi Low pH and High
affinity between KDEL and KDEL receptor exist, while in ER High pH

• Binding of the KDEL signal peptide in the lumen of the Golgi results in
structural changes in the cytoplasmic face of the receptor, which signals
to COPI coatomer to bind and initiate trafficking back to the ER
 Cell Biology:
Vesicular Fusion
Dr. Amit Joshi
HOD & Assistant Professor
Biochemistry Department
KALINGA UNIVERSITY
Naya Raipur, CG, INDIA-492101
 Cell Biology:
Nuclear Transport
Dr. Amit Joshi
HOD & Assistant Professor
Biochemistry Department
KALINGA UNIVERSITY
Naya Raipur, CG, INDIA-492101
 Cell Biology:
ABO Blood Group
Biochemistry
Dr. Amit Joshi
HOD
BIOCHEMISTRY DEPARTMENT
KALINGA UNIVERSITY
Naya Raipur, CG, INDIA-492101
 Cell Biology:
Ubiquitinization of Proteins
Dr. Amit Joshi
HOD
BIOCHEMISTRY DEPARTMENT
KALINGA UNIVERSITY
Naya Raipur, CG, INDIA-492101
•Questions