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Staphylococcal display for combinatorial protein engineering of a head-to-tail affibody dimer binding the Alzheimer amyloid-ss peptide
KTH, School of Biotechnology (BIO), Molecular Biotechnology (closed 20130101).ORCID iD: 0000-0002-5192-7362
KTH, School of Biotechnology (BIO), Molecular Biotechnology (closed 20130101).
KTH, School of Biotechnology (BIO), Molecular Biotechnology (closed 20130101).ORCID iD: 0000-0002-9282-0174
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2013 (English)In: Biotechnology Journal, ISSN 1860-6768, E-ISSN 1860-7314, Vol. 8, no 1, 139-145 p.Article in journal (Refereed) Published
Abstract [en]

We have previously generated an affibody molecule for the disease-associated amyloid beta (A beta) peptide, which has been shown to inhibit the formation of various A beta aggregates and revert the neurotoxicity of A beta in a fruit fly model of Alzheimer's disease. In this study, we have investigated a new bacterial display system for combinatorial protein engineering of the A beta-binder as a head-to-tail dimeric construct for future optimization efforts, e.g. affinity maturation. Using the bacterial display platform, we have: (i) demonstrated functional expression of the dimeric binder on the cell surface, (ii) determined the affinity and investigated the pH sensitivity of the interaction, (iii) demonstrated the importance of an intramolecular disulfide bond through selections from a cell-displayed combinatorial library, as well as (iv) investigated the effects from rational truncation of the N-terminal part of the affibody molecule on surface expression level and A beta binding. Overall, the detailed engineering and characterization of this promising A beta-specific affibody molecule have yielded valuable insights concerning its unusual binding mechanism. The results also demonstrated that our bacterial display system is a suitable technology for future protein engineering and characterization efforts of homo- or heterodimeric affinity proteins.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2013. Vol. 8, no 1, 139-145 p.
Keyword [en]
Affibody molecules, Alzheimer's disease, Amyloid beta, Bacterial display, Combinatorial protein engineering
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-111860DOI: 10.1002/biot.201200228ISI: 000312989500022PubMedID: 22987778Scopus ID: 2-s2.0-84871749509OAI: oai:DiVA.org:kth-111860DiVA: diva2:587393
Funder
Swedish Research Council, 2009-5758VINNOVA, 2009-00179
Note

QC 20130207

Available from: 2013-01-14 Created: 2013-01-14 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Engineering of Affibody molecules targeting the Alzheimer’s-related amyloid β peptide
Open this publication in new window or tab >>Engineering of Affibody molecules targeting the Alzheimer’s-related amyloid β peptide
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2015. x, 107 p.
Series
TRITA-BIO-Report, ISSN 1654-2312 ; 2015:14
Keyword
Affibody molecules, Alzheimer’s disease, AD, amyloid beta, Aß, combinatorial protein engineering, staphylococcal surface display
National Category
Other Natural Sciences
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-173864 (URN)978-91-7595-663-3 (ISBN)
Public defence
2015-10-09, D3, Lindstedtsvägen 5, KTH, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20150922

Available from: 2015-09-22 Created: 2015-09-21 Last updated: 2015-09-22Bibliographically approved

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Lindberg, HannaStåhl, StefanLöfblom, John

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