PMID- 10648240
OWN - NLM
STAT- MEDLINE
DCOM- 20000317
LR  - 20181113
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 127
IP  - 4
DP  - 2000 Feb
TI  - BMP-binding modules in chordin: a model for signalling regulation in the
      extracellular space.
PG  - 821-30
AB  - A number of genetic and molecular studies have implicated Chordin in the
      regulation of dorsoventral patterning during gastrulation. Chordin, a BMP
      antagonist of 120 kDa, contains four small (about 70 amino acids each)
      cysteine-rich domains (CRs) of unknown function. In this study, we show that the 
      Chordin CRs define a novel protein module for the binding and regulation of BMPs.
      The biological activity of Chordin resides in the CRs, especially in CR1 and CR3,
      which have dorsalizing activity in Xenopus embryo assays and bind BMP4 with
      dissociation constants in the nanomolar range. The activity of individual CRs,
      however, is 5- to 10-fold lower than that of full-length Chordin. These results
      shed light on the molecular mechanism by which Chordin/BMP complexes are
      regulated by the metalloprotease Xolloid, which cleaves in the vicinity of CR1
      and CR3 and would release CR/BMP complexes with lower anti-BMP activity than
      intact Chordin. CR domains are found in other extracellular proteins such as
      procollagens. Full-length Xenopus procollagen IIA mRNA has dorsalizing activity
      in embryo microinjection assays and the CR domain is required for this activity. 
      Similarly, a C. elegans cDNA containing five CR domains induces secondary axes in
      injected Xenopus embryos. These results suggest that CR modules may function in a
      number of extracellular proteins to regulate growth factor signalling.
FAU - Larrain, J
AU  - Larrain J
AD  - Howard Hughes Medical Institute and Department of Biological Chemistry,
      University of California, Los Angeles, CA 90095-1662, USA.
FAU - Bachiller, D
AU  - Bachiller D
FAU - Lu, B
AU  - Lu B
FAU - Agius, E
AU  - Agius E
FAU - Piccolo, S
AU  - Piccolo S
FAU - De Robertis, E M
AU  - De Robertis EM
LA  - eng
GR  - R37 HD021502/HD/NICHD NIH HHS/United States
GR  - R37 HD021502-13/HD/NICHD NIH HHS/United States
GR  - R37 HD21502-13/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Procollagen)
RN  - 0 (Proteins)
RN  - 93586-27-7 (chordin)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Base Sequence
MH  - Binding Sites
MH  - Body Patterning
MH  - Bone Morphogenetic Proteins/antagonists & inhibitors/*metabolism
MH  - Caenorhabditis elegans/genetics
MH  - Cysteine/chemistry
MH  - DNA Primers/genetics
MH  - Gene Expression Regulation, Developmental
MH  - *Glycoproteins
MH  - *Intercellular Signaling Peptides and Proteins
MH  - Mice
MH  - *Models, Biological
MH  - Molecular Sequence Data
MH  - Procollagen/genetics/metabolism
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Proteins/chemistry/genetics/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - Xenopus/*embryology/genetics/*metabolism
PMC - PMC2280033
MID - NIHMS43285
EDAT- 2000/01/29 09:00
MHDA- 2000/03/25 09:00
CRDT- 2000/01/29 09:00
PHST- 2000/01/29 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/01/29 09:00 [entrez]
PST - ppublish
SO  - Development. 2000 Feb;127(4):821-30.