Journal Article

PUBDB-2024-07304

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Coupling of Spectrin Repeat Modules for the Assembly of Nanorods and Presentation of Protein Domains

Mezgec, K. (Corresponding author)Extern*EMBL* ; Snoj, J. ; Ulčakar, L. ; Ljubetič, A. ; Tušek Žnidarič, M. ; Škarabot, M. ; Jerala, R. (Corresponding author)

2024
Soc. Washington, DC

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Please use a persistent id in citations: doi:10.1021/acsnano.4c07701  doi:10.3204/PUBDB-2024-07304

Abstract: Modular protein engineering is a powerful approach for fabricating high-molecular-weight assemblies and biomaterials with nanoscale precision. Herein, we address the challenge of designing an extended nanoscale filamentous architecture inspired by the central rod domain of human dystrophin, which protects sarcolemma during muscle contraction and consists of spectrin repeats composed of three-helical bundles. A module of three tandem spectrin repeats was used as a rigid building block self-assembling via coiled-coil (CC) dimer-forming peptides. CC peptides were precisely integrated to maintain the spectrin α-helix continuity in an appropriate frame to form extended nanorods. An orthogonal set of customizable CC heterodimers was harnessed for modular rigid domain association, which could be additionally regulated by metal ions and chelators. We achieved a robust assembly of rigid rods several micrometers in length, determined by atomic force microscopy and negative stain transmission electron microscopy. Furthermore, these rigid rods can serve as a scaffold for the decoration of diverse proteins or biologically active peptides along their length with adjustable spacing up to tens of nanometers, as confirmed by the DNA-PAINT super-resolution microscopy. This demonstrates the potential of modular bottom-up protein engineering and tunable CCs for the fabrication of functionalized protein biomaterials.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. CTGCT - Centre of Excellence for the Technologies of Gene and Cell Therapy (101059842) (101059842)
3. LoopOfFun - Closed-loop control of fungal materials (101070817) (101070817)
4. VIROFIGHT - General-purpose virus-neutralizing engulfing shells with modular target-specificity (899619) (899619)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)

Appears in the scientific report 2024

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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