PMID- 19114710
OWN - NLM
STAT- MEDLINE
DCOM- 20090427
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 284
IP  - 10
DP  - 2009 Mar 6
TI  - The binding properties of minimal oligosaccharides reveal a common heparan 
      sulfate/dermatan sulfate-binding site in hepatocyte growth factor/scatter factor 
      that can accommodate a wide variety of sulfation patterns.
PG  - 6311-21
LID - 10.1074/jbc.M807671200 [doi]
AB  - Heparan sulfate (HS)/heparin and dermatan sulfate (DS) both bind with high 
      affinity to hepatocyte growth factor/scatter factor (HGF/SF) and function as 
      necessary co-factors in vitro. How both these two structurally distinct 
      glycosaminoglycans (GAGs) are recognized has remained unclear. We have now 
      reconciled this issue using a panel of minimal tri- and tetrasaccharide sequences 
      of variable but well defined sulfation patterns in combination with further 
      development of the gel mobility shift assay to allow simultaneous comparisons of 
      relative protein affinities/selectivities for different oligosaccharides. From 
      this approach it would seem that a minimum binding sequence is a disulfated 
      trisaccharide comprised of an internal iduronate flanked by monosulfated 
      hexosamine residues and that additional sulfation further enhances affinity. 
      However, the similarity in recognition of HS/heparin and DS seems to arise 
      primarily from a lack of any apparent positional requirement for sulfation. Thus, 
      isomers of HS/heparin tetrasaccharides containing only two sulfates irrespective 
      of whether they are purely N-, 2-O-, or 6-O-sulfates bind with equivalent 
      apparent affinity as a disulfated DS tetrasaccharide. In addition, the NMR 
      chemical shifts induced in NK1 (the truncated variant of HGF/SF comprised of the 
      N-terminal and first Kringle domains) by titration with either heparin or DS 
      oligosaccharides strongly indicate that both bind to essentially the same site. 
      Together, these observations reveal an unexpected degree of flexibility in the 
      GAG-HGF/SF interface, allowing a single binding site in the protein to 
      accommodate iduronate-containing sequences of variable sulfation pattern and/or 
      density from different GAGs.
FAU - Deakin, Jon A
AU  - Deakin JA
AD  - Cancer Research UK Glyco-Oncology Group, School of Cancer and Imaging Sciences, 
      Paterson Institute for Cancer Research, University of Manchester, Wilmslow Rd., 
      Manchester M20 4BX, United Kingdom.
FAU - Blaum, Barbel S
AU  - Blaum BS
FAU - Gallagher, John T
AU  - Gallagher JT
FAU - Uhrin, Dusan
AU  - Uhrin D
FAU - Lyon, Malcolm
AU  - Lyon M
LA  - eng
GR  - Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081229
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HGF protein, human)
RN  - 0 (Oligosaccharides)
RN  - 24967-94-0 (Dermatan Sulfate)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9050-30-0 (Heparitin Sulfate)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Cricetinae
MH  - Cricetulus
MH  - Dermatan Sulfate/*chemistry/metabolism
MH  - Heparitin Sulfate/*chemistry/metabolism
MH  - Hepatocyte Growth Factor/*chemistry/genetics/metabolism
MH  - Humans
MH  - Oligosaccharides/*chemistry/metabolism
MH  - Protein Binding/physiology
MH  - Protein Structure, Tertiary/physiology
EDAT- 2008/12/31 09:00
MHDA- 2009/04/28 09:00
CRDT- 2008/12/31 09:00
PHST- 2008/12/31 09:00 [entrez]
PHST- 2008/12/31 09:00 [pubmed]
PHST- 2009/04/28 09:00 [medline]
AID - S0021-9258(20)32659-4 [pii]
AID - 10.1074/jbc.M807671200 [doi]
PST - ppublish
SO  - J Biol Chem. 2009 Mar 6;284(10):6311-21. doi: 10.1074/jbc.M807671200. Epub 2008 
      Dec 29.