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

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The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement anchor. / Bengtsson, Eva; Mörgelin, Matthias; Sasaki, Takako; Timpl, Rupert; Heinegård, Dick; Aspberg, Anders.

In: Journal of Biological Chemistry, Vol. 277, No. 17, 2002, p. 15061-15068.

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Bengtsson, Eva ; Mörgelin, Matthias ; Sasaki, Takako ; Timpl, Rupert ; Heinegård, Dick ; Aspberg, Anders. / The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement anchor. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 17. pp. 15061-15068.

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TY - JOUR

T1 - The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement anchor.

AU - Bengtsson, Eva

AU - Mörgelin, Matthias

AU - Sasaki, Takako

AU - Timpl, Rupert

AU - Heinegård, Dick

AU - Aspberg, Anders

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Connective Tissue Biology (013230151), Department of Experimental Medical Science (013210000), Experimental Cardiovascular Research Unit (013242110), Division of Infection Medicine (BMC) (013024020)

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Extracellular Matrix Proteins/metabolism

KW - Collagen/metabolism

KW - Glycoproteins/metabolism

KW - Heparan Sulfate Proteoglycan/metabolism

KW - Protein Binding

KW - Mice

KW - Basement Membrane/metabolism

KW - Animal

U2 - 10.1074/jbc.M108285200

DO - 10.1074/jbc.M108285200

M3 - Article

VL - 277

SP - 15061

EP - 15068

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 17

ER -