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The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement anchor.

Bengtsson, Eva LU ; Mörgelin, Matthias LU ; Sasaki, Takako; Timpl, Rupert; Heinegård, Dick LU and Aspberg, Anders LU (2002) In Journal of Biological Chemistry 277(17). p.15061-15068
Abstract
PRELP is a heparin-binding leucine-rich repeat protein in connective tissue extracellular matrix. In search of natural ligands and biological functions of this molecule, we found that PRELP binds the basement membrane heparan sulfate proteoglycan perlecan. Also recombinant perlecan domains I and V carrying heparan sulfate bound PRELP, whereas other domains without glycosaminoglycan substitution did not. Heparin, but not chondroitin sulfate, inhibited the interactions. Glycosaminoglycan-free recombinant perlecan domain V and mutated domain I did not bind PRELP. The dissociation constants of the PRELP-perlecan interactions were in the range of 3-18 nM as determined by surface plasmon resonance. As expected, truncated PRELP, without the... (More)
PRELP is a heparin-binding leucine-rich repeat protein in connective tissue extracellular matrix. In search of natural ligands and biological functions of this molecule, we found that PRELP binds the basement membrane heparan sulfate proteoglycan perlecan. Also recombinant perlecan domains I and V carrying heparan sulfate bound PRELP, whereas other domains without glycosaminoglycan substitution did not. Heparin, but not chondroitin sulfate, inhibited the interactions. Glycosaminoglycan-free recombinant perlecan domain V and mutated domain I did not bind PRELP. The dissociation constants of the PRELP-perlecan interactions were in the range of 3-18 nM as determined by surface plasmon resonance. As expected, truncated PRELP, without the heparin-binding domain, did not bind perlecan. Confocal immunohistochemistry showed that PRELP outlines basement membranes with a location adjacent to perlecan. We also found that PRELP binds collagen type I and type II through its leucine-rich repeat domain. Electron microscopy visualized a complex with PRELP binding simultaneously to the triple helical region of procollagen I and the heparan sulfate chains of perlecan. Based on the location of PRELP and its interaction with perlecan heparan sulfate chains and collagen, we propose a function of PRELP as a molecule anchoring basement membranes to the underlying connective tissue. (Less)
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organization
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Contribution to journal
publication status
published
subject
keywords
Extracellular Matrix Proteins/*metabolism, Collagen/*metabolism, Glycoproteins/*metabolism, Heparan Sulfate Proteoglycan/*metabolism, Protein Binding, Mice, Basement Membrane/metabolism, Animal
in
Journal of Biological Chemistry
volume
277
issue
17
pages
15061 - 15068
publisher
ASBMB
external identifiers
  • wos:000175203000090
  • scopus:0037177893
ISSN
1083-351X
DOI
10.1074/jbc.M108285200
language
English
LU publication?
yes
id
45ee8e04-b0b5-4119-a98a-9b488aa3ef3d (old id 105989)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11847210&dopt=Abstract
date added to LUP
2007-07-10 11:24:52
date last changed
2017-07-23 03:40:13
@article{45ee8e04-b0b5-4119-a98a-9b488aa3ef3d,
  abstract     = {PRELP is a heparin-binding leucine-rich repeat protein in connective tissue extracellular matrix. In search of natural ligands and biological functions of this molecule, we found that PRELP binds the basement membrane heparan sulfate proteoglycan perlecan. Also recombinant perlecan domains I and V carrying heparan sulfate bound PRELP, whereas other domains without glycosaminoglycan substitution did not. Heparin, but not chondroitin sulfate, inhibited the interactions. Glycosaminoglycan-free recombinant perlecan domain V and mutated domain I did not bind PRELP. The dissociation constants of the PRELP-perlecan interactions were in the range of 3-18 nM as determined by surface plasmon resonance. As expected, truncated PRELP, without the heparin-binding domain, did not bind perlecan. Confocal immunohistochemistry showed that PRELP outlines basement membranes with a location adjacent to perlecan. We also found that PRELP binds collagen type I and type II through its leucine-rich repeat domain. Electron microscopy visualized a complex with PRELP binding simultaneously to the triple helical region of procollagen I and the heparan sulfate chains of perlecan. Based on the location of PRELP and its interaction with perlecan heparan sulfate chains and collagen, we propose a function of PRELP as a molecule anchoring basement membranes to the underlying connective tissue.},
  author       = {Bengtsson, Eva and Mörgelin, Matthias and Sasaki, Takako and Timpl, Rupert and Heinegård, Dick and Aspberg, Anders},
  issn         = {1083-351X},
  keyword      = {Extracellular Matrix Proteins/*metabolism,Collagen/*metabolism,Glycoproteins/*metabolism,Heparan Sulfate Proteoglycan/*metabolism,Protein Binding,Mice,Basement Membrane/metabolism,Animal},
  language     = {eng},
  number       = {17},
  pages        = {15061--15068},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement anchor.},
  url          = {http://dx.doi.org/10.1074/jbc.M108285200},
  volume       = {277},
  year         = {2002},
}