Synthetic human prion protein octapeptide repeat binds to the proteinase K active site

Dessislava Georgieva; Wojciech Rypniewski; Hartmut Echner; Markus Perbandt; Mirjam Koker; Joachim Clos; Lars Redecke; Reinhard Bredehorst; Wolfgang Voelter; Nicolay Genov; Christian Betzel

doi:10.1016/j.bbrc.2004.10.184

Synthetic human prion protein octapeptide repeat binds to the proteinase K active site

Dessislava Georgieva
, Wojciech Rypniewski
, Hartmut Echner
, Markus Perbandt
, Mirjam Koker
, Joachim Clos
, Lars Redecke
, Reinhard Bredehorst
, Wolfgang Voelter
, Nicolay Genov
, Christian Betzel

Institut für Biochemie

Universitätsklinikum Hamburg-Eppendorf
Bernhard Nocht Institute for Tropical Medicine
Universität Hamburg
Bulgarian Academy of Sciences

8 Zitate (Scopus)

Abstract

Proteinase K is widely used in tests for the presence of infectious prion protein causing fatal spongiform encephalopathies. To investigate possible interactions between the enzyme and the functionally important N-terminal prion domain, we crystallized mercury-inhibited proteinase K in the presence of the synthetic peptides GGGWGQPH and HGGGW. The octapeptide sequence is identical to that of a single octapeptide repeat (OPR) from the physiologically important OPR region. Here, we present the first direct evidence for the complex formation between a proteolytic enzyme and a segment of human prion molecule. The X-ray structures of the complexes at 1.4 and 1.8 Å resolution, respectively, revealed that in both cases the segment GGG is strongly bound as a real substrate at the substrate recognition site of the proteinase forming an antiparallel β-strand between the two parallel strands of Asn99-Tyr104 and Ser132-Gly136. The complex is stabilized through an extended H-bonding network.

Originalsprache	Englisch
Zeitschrift	Biochemical and Biophysical Research Communications
Jahrgang	325
Ausgabenummer	4
Seiten (von - bis)	1406-1411
Seitenumfang	6
ISSN	0006-291X
DOIs	https://doi.org/10.1016/j.bbrc.2004.10.184
Publikationsstatus	Veröffentlicht - 24.12.2004

Fördermittel

The authors thank the Deutsche Luft- und Raumfahrtagentur (DLR, Projektträger Gesundheitsforschung, Grant 01KO0206) and the RiNA GmbH Berlin for financial support. This work was supported in part by the Bulgarian National Foundation for Scientific Research, Grant X-1301. Ch. Betzel thanks the Deutsche Forschungsgemeinschaft for the financial support during a visit at the Institute of Organic Chemistry, Bulgarian Academy of Sciences, under contract 436 BUL 113/115/8-1.

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SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

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10.1016/j.bbrc.2004.10.184

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title = "Synthetic human prion protein octapeptide repeat binds to the proteinase K active site",

abstract = "Proteinase K is widely used in tests for the presence of infectious prion protein causing fatal spongiform encephalopathies. To investigate possible interactions between the enzyme and the functionally important N-terminal prion domain, we crystallized mercury-inhibited proteinase K in the presence of the synthetic peptides GGGWGQPH and HGGGW. The octapeptide sequence is identical to that of a single octapeptide repeat (OPR) from the physiologically important OPR region. Here, we present the first direct evidence for the complex formation between a proteolytic enzyme and a segment of human prion molecule. The X-ray structures of the complexes at 1.4 and 1.8 {\AA} resolution, respectively, revealed that in both cases the segment GGG is strongly bound as a real substrate at the substrate recognition site of the proteinase forming an antiparallel β-strand between the two parallel strands of Asn99-Tyr104 and Ser132-Gly136. The complex is stabilized through an extended H-bonding network.",

author = "Dessislava Georgieva and Wojciech Rypniewski and Hartmut Echner and Markus Perbandt and Mirjam Koker and Joachim Clos and Lars Redecke and Reinhard Bredehorst and Wolfgang Voelter and Nicolay Genov and Christian Betzel",

note = "Funding Information: The authors thank the Deutsche Luft- und Raumfahrtagentur (DLR, Projekttr{\"a}ger Gesundheitsforschung, Grant 01KO0206) and the RiNA GmbH Berlin for financial support. This work was supported in part by the Bulgarian National Foundation for Scientific Research, Grant X-1301. Ch. Betzel thanks the Deutsche Forschungsgemeinschaft for the financial support during a visit at the Institute of Organic Chemistry, Bulgarian Academy of Sciences, under contract 436 BUL 113/115/8-1. Copyright: Copyright 2012 Elsevier B.V., All rights reserved.",

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AU - Georgieva, Dessislava

AU - Rypniewski, Wojciech

AU - Echner, Hartmut

AU - Perbandt, Markus

AU - Koker, Mirjam

AU - Clos, Joachim

AU - Redecke, Lars

AU - Bredehorst, Reinhard

AU - Voelter, Wolfgang

AU - Genov, Nicolay

AU - Betzel, Christian

N1 - Funding Information: The authors thank the Deutsche Luft- und Raumfahrtagentur (DLR, Projektträger Gesundheitsforschung, Grant 01KO0206) and the RiNA GmbH Berlin for financial support. This work was supported in part by the Bulgarian National Foundation for Scientific Research, Grant X-1301. Ch. Betzel thanks the Deutsche Forschungsgemeinschaft for the financial support during a visit at the Institute of Organic Chemistry, Bulgarian Academy of Sciences, under contract 436 BUL 113/115/8-1. Copyright: Copyright 2012 Elsevier B.V., All rights reserved.

PY - 2004/12/24

Y1 - 2004/12/24

N2 - Proteinase K is widely used in tests for the presence of infectious prion protein causing fatal spongiform encephalopathies. To investigate possible interactions between the enzyme and the functionally important N-terminal prion domain, we crystallized mercury-inhibited proteinase K in the presence of the synthetic peptides GGGWGQPH and HGGGW. The octapeptide sequence is identical to that of a single octapeptide repeat (OPR) from the physiologically important OPR region. Here, we present the first direct evidence for the complex formation between a proteolytic enzyme and a segment of human prion molecule. The X-ray structures of the complexes at 1.4 and 1.8 Å resolution, respectively, revealed that in both cases the segment GGG is strongly bound as a real substrate at the substrate recognition site of the proteinase forming an antiparallel β-strand between the two parallel strands of Asn99-Tyr104 and Ser132-Gly136. The complex is stabilized through an extended H-bonding network.

AB - Proteinase K is widely used in tests for the presence of infectious prion protein causing fatal spongiform encephalopathies. To investigate possible interactions between the enzyme and the functionally important N-terminal prion domain, we crystallized mercury-inhibited proteinase K in the presence of the synthetic peptides GGGWGQPH and HGGGW. The octapeptide sequence is identical to that of a single octapeptide repeat (OPR) from the physiologically important OPR region. Here, we present the first direct evidence for the complex formation between a proteolytic enzyme and a segment of human prion molecule. The X-ray structures of the complexes at 1.4 and 1.8 Å resolution, respectively, revealed that in both cases the segment GGG is strongly bound as a real substrate at the substrate recognition site of the proteinase forming an antiparallel β-strand between the two parallel strands of Asn99-Tyr104 and Ser132-Gly136. The complex is stabilized through an extended H-bonding network.

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Synthetic human prion protein octapeptide repeat binds to the proteinase K active site

Abstract

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