PMID- 8812649
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1095-9130 (Electronic)
IS  - 1046-2023 (Linking)
VI  - 10
IP  - 1
DP  - 1996 Aug
TI  - MCP-1: Structure/Activity Analysis.
PG  - 93-103
AB  - Structure/activity relationships underlying the function of monocyte 
      chemoattractant protein-1 (MCP-1) have been probed by site-directed mutagenesis 
      and indicate that the N-terminus of MCP-1 plays a critical role in activating the 
      MCP-1 receptor, especially aspartate-3. However, a monocyte chemoattractant motif 
      analogous to the ELR sequence of neutrophil-active chemokines has not yet been 
      identified. Amino acids whose side chains project from one face of the first 
      beta-pleated sheet of MCP-1 are also involved in biological activity as is 
      arginine-24. Among C-C chemokines, position 24 is occupied by arginine only in 
      MCP-1, -2, and -3, suggesting that arginine may be a substitution specific for 
      monocyte chemoattractants. Several MCP-1 variants antagonize wild-type MCP-1 
      activity, the most potent being N-terminal deletion variants. One such variant 
      lacking amino acids 2-8 (called 7ND) inhibits monocyte chemotaxis in response to 
      wild-type MCP-1, but not in response to chemically crosslinked MCP-1 homodimers. 
      This indicates that N-terminal deletion variants exert their effects as dominant 
      negative inhibitors, which implies that MCP-1 activates its receptor as a dimer. 
      This has profound biological implications and also suggests that the dimer 
      interface may be a target for MCP-1 inhibitors. Finally, mutagenesis has 
      demonstrated that murine MCP-1 consists of two domains. An N-terminal domain 
      colinear with human MCP-1 contains all of murine MCP-1's chemoattractant 
      activity. A C-terminal domain of 49 amino acids, which is rich in serine and 
      threonine, contains an extensive amount of O-linked carbohydrate that accounts 
      for 50% of murine MCP-1's apparent molecular size.
FAU - Zhang, Y
AU  - Zhang Y
AD  - Department of Medicine, Harvard Medical School, Boston, Massachusetts, 02115
FAU - Ernst, CA
AU  - Ernst CA
FAU - Rollins, BJ
AU  - Rollins BJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Methods
JT  - Methods (San Diego, Calif.)
JID - 9426302
EDAT- 1996/08/01 00:00
MHDA- 1996/08/01 00:01
CRDT- 1996/08/01 00:00
PHST- 1996/08/01 00:00 [pubmed]
PHST- 1996/08/01 00:01 [medline]
PHST- 1996/08/01 00:00 [entrez]
AID - S1046202396900833 [pii]
AID - 10.1006/meth.1996.0083 [doi]
PST - ppublish
SO  - Methods. 1996 Aug;10(1):93-103. doi: 10.1006/meth.1996.0083.