Journal Article

PUBDB-2026-01498

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Native mass spectrometry meets X-rays for the elucidation of protein structures

Kierspel, T.CSSB*DESY* ; De Santis, E.Extern*XFEL.EU* ; Schamoni-Kast, K.Extern*CSSB*XFEL.EU* ; Blanchet, C.Extern*EMBL* ; Marklund, E.Extern* ; Caleman, C.CFEL*DESY* ; Uetrecht, C. (Corresponding author)CSSB*XFEL.EU*DESY*

2026
Portland Press London

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Please use a persistent id in citations: doi:10.1042/BST20250111  doi:10.3204/PUBDB-2026-01498

Abstract: Small-angle X-ray scattering (SAXS) is a powerful and widely used technique for structural biology, providing information about solution structures, i.e., without the need for crystallization or cryogenic conditions. However, its applicability is limited in cases where sample heterogeneity, conformational mixtures, or aggregation are present. While modern BioSAXS routinely employs inline purification (e.g., SEC-SAXS) to address heterogeneity, gas-phase SAXS, enabled by native mass spectrometry as a sample delivery method, offers an even higher degree of population selectivity by providing well-defined and mass-selected ion populations. The principal challenge of this approach is the inherently low particle density in the gas phase. In the present overview, we present simulations of gas-phase SAXS viral nonstructural proteins and capsids and compare them against diffraction patterns from prototypical GroEL. We evaluate the expected scattering signal under experimentally realistic conditions and discuss potential implementations and use cases at both synchrotron radiation sources and X-ray free-electron lasers, thereby outlining regimes in which gas-phase SAXS may become a viable complementary tool for structural studies.

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Contributing Institute(s):

1. CSSB - Leibniz-Institut für Experimentelle Virologie (LIV) / DESY - Charlotte Uetrecht (CSSB-LIV/DESY-CU)
2. FS-CFEL-1 (Group Leader: Henry Chapman) (CFEL-I)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)
2. 05K22PSA - Verbundprojekt 05K2022 - 2021-05988 SAXFELS: Kleinwinkel-Röntgen-Freie-Elektronenlaser-Streuung (BMBF-05K22PSA) (BMBF-05K22PSA)
3. SPIDoc's - The Next Generation MS SPIDoc’s (101120312) (101120312)
4. ARIADNE - Redefining mass spectrometry – a breakthrough platform for real-time noninvasive breath analysis with single ion detection of intact viruses and bacteria and post-analysis molecular characterization (964553) (964553)

Experiment(s):

1. No specific instrument

Appears in the scientific report 2026

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Database coverage:
; ; ; Allianz-Lizenz / DFG ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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