PMID- 9792674
OWN - NLM
STAT- MEDLINE
DCOM- 19981210
LR  - 20220409
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 45
DP  - 1998 Nov 6
TI  - Lysine 58 and histidine 66 at the C-terminal alpha-helix of monocyte 
      chemoattractant protein-1 are essential for glycosaminoglycan binding.
PG  - 29641-7
AB  - Monocytes rolling on the endothelial cell layer interact with monocyte 
      chemoattractant protein-1 (MCP-1) that is tethered to the proteoglycans on the 
      luminal side of the endothelial cells and consequently initiate adhesion of 
      monocytes in the early phase of immune response. The amino acid residues in MCP-1 
      involved in tethering to the proteoglycans have not been elucidated. MCP-1 showed 
      binding to [3H]heparin with a KD of 1.5 microM. We substituted lysine or 
      histidine residues at the C-terminal end of MCP-1 with alanine residues and 
      tested these mutants for their ability to bind heparin, heparan sulfate, 
      hyaluronic acid, and chondroitin sulfate-C. Substitution of Lys-58 or His-66 
      drastically reduced glycosaminoglycan binding. Substitution of Lys-56 or deletion 
      of the five amino acid residues at the C terminus, including Lys-75, did not 
      alter the heparin binding ability, suggesting that the other lysine residues at 
      the C terminus are not involved in glycosaminoglycan binding. MCP-1 and its 
      mutants did not bind hyaluronic acid as strongly as the other subunits of the 
      GAGs. Substitution of Lys-58 or His-66 by alanine that prevented 
      glycosaminoglycan binding did not affect Ca2+ influx, receptor binding, or 
      chemotactic activity elicited by the chemokine on monocytic THP-1 cells. 
      Therefore, we conclude that the Lys-58 and His-66 residues in the C-terminal 
      alpha-helix of MCP-1 are essential for glycosaminoglycan binding and probably for 
      the binding to the endothelial surface proteoglycans.
FAU - Chakravarty, L
AU  - Chakravarty L
AD  - Neurobiotechnology Center and the Departments of Biochemistry and Medical 
      Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.
FAU - Rogers, L
AU  - Rogers L
FAU - Quach, T
AU  - Quach T
FAU - Breckenridge, S
AU  - Breckenridge S
FAU - Kolattukudy, P E
AU  - Kolattukudy PE
LA  - eng
GR  - HL48916/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glycosaminoglycans)
RN  - 4QD397987E (Histidine)
RN  - K3Z4F929H6 (Lysine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding, Competitive
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Chemokine CCL2/chemistry/*metabolism
MH  - Chemotaxis, Leukocyte
MH  - Glycosaminoglycans/*metabolism
MH  - Histidine/*metabolism
MH  - Humans
MH  - Ion Transport
MH  - Lysine/*metabolism
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Spodoptera
EDAT- 1998/10/29 00:00
MHDA- 1998/10/29 00:01
CRDT- 1998/10/29 00:00
PHST- 1998/10/29 00:00 [pubmed]
PHST- 1998/10/29 00:01 [medline]
PHST- 1998/10/29 00:00 [entrez]
AID - S0021-9258(19)59363-2 [pii]
AID - 10.1074/jbc.273.45.29641 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Nov 6;273(45):29641-7. doi: 10.1074/jbc.273.45.29641.