Structural and biophysical characterisation of agrin laminin G3 domain constructs

Henning Tidow; Daniel Mattle; Poul Nissen

doi:10.1093/protein/gzq082

Structural and biophysical characterisation of agrin laminin G3 domain constructs

Henning Tidow
, Daniel Mattle
, Poul Nissen

Institut for Molekylærbiologi og Genetik

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

6 Citationer (Scopus)

Abstract

Agrin mediates accumulation of acetylcholine receptors (AChRs) at the developing neuromuscular junction, but has also been implicated as a regulator of central nervous system (CNS) synapses. A C-terminal region of agrin (Ag-C20) binds to the α3 subunit of the sodium-potassium ATPase (NKA) in CNS neurons suggesting that α3NKA is a neuronal agrin receptor, whereas a shorter agrin fragment (Ag-C15) was shown to act as a competitive antagonist. Here, we show that the agrin C22 construct, which represents the naturally occurring neurotrypsin cleavage product, constitutes a well-folded, stable domain, while the deletion of 48 residues that correspond to strands β1-β4 of the agrin laminin G3 domain imposed by the agrin C15 construct leads to a misfolded protein.

Originalsprog	Engelsk
Tidsskrift	Protein Engineering Design and Selection (Print)
Vol/bind	24
Nummer	1-2
Sider (fra-til)	219-224
Antal sider	6
ISSN	1741-0126
DOI	https://doi.org/10.1093/protein/gzq082
Status	Udgivet - 2011

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@article{3446c226ef294460973e2107eb4df233,

title = "Structural and biophysical characterisation of agrin laminin G3 domain constructs",

abstract = "Agrin mediates accumulation of acetylcholine receptors (AChRs) at the developing neuromuscular junction, but has also been implicated as a regulator of central nervous system (CNS) synapses. A C-terminal region of agrin (Ag-C20) binds to the α3 subunit of the sodium-potassium ATPase (NKA) in CNS neurons suggesting that α3NKA is a neuronal agrin receptor, whereas a shorter agrin fragment (Ag-C15) was shown to act as a competitive antagonist. Here, we show that the agrin C22 construct, which represents the naturally occurring neurotrypsin cleavage product, constitutes a well-folded, stable domain, while the deletion of 48 residues that correspond to strands β1-β4 of the agrin laminin G3 domain imposed by the agrin C15 construct leads to a misfolded protein.",

keywords = "Agrin, Amino Acid Sequence, Animals, Chickens, Laminin, Mice, Models, Molecular, Molecular Sequence Data, Protein Folding, Protein Stability, Protein Structure, Tertiary, Sequence Alignment, Sequence Deletion",

author = "Henning Tidow and Daniel Mattle and Poul Nissen",

year = "2011",

doi = "10.1093/protein/gzq082",

language = "English",

volume = "24",

pages = "219--224",

journal = "Protein Engineering Design and Selection (Print)",

issn = "1741-0126",

publisher = "Oxford University Press",

number = "1-2",

}

TY - JOUR

T1 - Structural and biophysical characterisation of agrin laminin G3 domain constructs

AU - Tidow, Henning

AU - Mattle, Daniel

AU - Nissen, Poul

PY - 2011

Y1 - 2011

N2 - Agrin mediates accumulation of acetylcholine receptors (AChRs) at the developing neuromuscular junction, but has also been implicated as a regulator of central nervous system (CNS) synapses. A C-terminal region of agrin (Ag-C20) binds to the α3 subunit of the sodium-potassium ATPase (NKA) in CNS neurons suggesting that α3NKA is a neuronal agrin receptor, whereas a shorter agrin fragment (Ag-C15) was shown to act as a competitive antagonist. Here, we show that the agrin C22 construct, which represents the naturally occurring neurotrypsin cleavage product, constitutes a well-folded, stable domain, while the deletion of 48 residues that correspond to strands β1-β4 of the agrin laminin G3 domain imposed by the agrin C15 construct leads to a misfolded protein.

AB - Agrin mediates accumulation of acetylcholine receptors (AChRs) at the developing neuromuscular junction, but has also been implicated as a regulator of central nervous system (CNS) synapses. A C-terminal region of agrin (Ag-C20) binds to the α3 subunit of the sodium-potassium ATPase (NKA) in CNS neurons suggesting that α3NKA is a neuronal agrin receptor, whereas a shorter agrin fragment (Ag-C15) was shown to act as a competitive antagonist. Here, we show that the agrin C22 construct, which represents the naturally occurring neurotrypsin cleavage product, constitutes a well-folded, stable domain, while the deletion of 48 residues that correspond to strands β1-β4 of the agrin laminin G3 domain imposed by the agrin C15 construct leads to a misfolded protein.

KW - Agrin

KW - Amino Acid Sequence

KW - Animals

KW - Chickens

KW - Laminin

KW - Mice

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Protein Folding

KW - Protein Stability

KW - Protein Structure, Tertiary

KW - Sequence Alignment

KW - Sequence Deletion

U2 - 10.1093/protein/gzq082

DO - 10.1093/protein/gzq082

M3 - Journal article

C2 - 21037280

SN - 1741-0126

VL - 24

SP - 219

EP - 224

JO - Protein Engineering Design and Selection (Print)

JF - Protein Engineering Design and Selection (Print)

IS - 1-2

ER -

Structural and biophysical characterisation of agrin laminin G3 domain constructs

Abstract

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