Publications

GBPs are dynamin-like GTPases that act as core orchestrators of the cell-autonomous immune response by coating the membranes of intracellular pathogen replication niches and/or cytosol-invasive gram-negative bacteria. We used cryo-EM/cryo-ET to resolve the molecular ultrastructure of GBP1 coatomers and reveal the large-scale conformational changes that allow GBP1 to selectively target LPS-containing membranes. We further demonstrate, for the first time, that GTP hydrolysis drives GBP1-dependent membrane fragmentation, which possibly underlies the ability to recruit and activate caspase4-dependent inflammasomes.

Kuhm T, Taisne CM, de Agrela Pinto C, Gross L, Giannopolou EA, Huber ST, Pardon E, Steyaert J, Tans S, Jakobi AJ

Nature Structural & Molecular Biology 32:172–184 (2025)

Associated data/code:           

PDBe: 8cqb

EMDB: EMD-16813, EMD-16814, EMD-16815, EMD-16794

Featured as NSMB Research Briefing.

Highlighted in the microbiologist, TU Delft News, phys.org.

Gas vesicles are nanoscale buoyancy compartments that form a unique motility system in (aquatic) bacteria and archaea. Using cryo-EM, we reveal the first molecular structure of the intact gas vesicle shell at 3.2 Å resolution. Our structure explains the molecular details underlying their unique properties such as the selective permeability of the shell and the role of structural reinforcement elements, consolidating decades of biochemical and biophysical studies. Our structure also allows to formulate a testable hypothesis of the intrigiuing structural program of gas vesicle assembly and growth.

Huber ST, Terwiel D, Evers W, Maresca D^#, Jakobi AJ^#

Cell 186:975-986 (2023)

Associated data/code:         

PDBe: 7r1c

EMDB: EMD-14238

Featured as News & Views in Nature Structural & Molecular Biology by Katarzyna Ciazynska.

Highlighted in TU Delft News and phys.org

We have developed a microelectromechanical system (MEMS) in which macromolecular targets are enclosed in nanofluidic channels formed between ultrathin, electron-transparent membranes. We show that these devices are suitable for high-resolution 3D structure determination of macromolecular complexes from picoliter sample volumes. Our device protects the sample from a destructive air-water interface and provides excellent control over geometric parameters of the nanochannels which yields uniform ice thickness.

Huber ST, Sarajilic E, Huijink R, Evers WH, Jakobi AJ

eLife 11:e72629 (2022)

Associated data/code:         

PDB: 7ohf

EMDB: EMD-12901, EMD-12902, EMD-12903, EMD-12914, EMD-12915, EMD-12917

Methods to improve interpretation of electrostatic potential maps from cryo-EM reconstructions are essential to build accurate atomic models. For all downstream applications it is important that any form of manipulation of these maps retains the physical properties expected from scattering of biological macromolecules. In this article we provide a roadmap to utilising such information to restrain the process of map sharpening and discuss its potential and limitations.

Bharadwaj A, Jakobi AJ

Faraday Discussions 11:e72629 (2022)

Associated data/code:         

PDBe: 6y5a

EMDB: EMD-10692

This article is discussed in the companion General Discussion of the RSC Faraday Meeting.

Thickness and quality controlled fabrication of fluorescence-targeted frozen-hydrated lamellae

Boltje DB, Skoupý R, Taisne CM, Evers WH, Jakobi AJ^#, Hoogenboom JP^#

Cell Reports Methods 5:101004 (2025)

Associated data/code:       

Enterovirus-like particles encapsidate RNA and exhibit decreased stability due to lack of maturation

Kuijpers L, Giannopoulou EA, Feng Y, van den Braak W, Freydoonian A, Ramlal R, Meiring H, Solano B, Roos W, Jakobi AJ, van der Pool LA, Dekker NH

PLoS Pathogens 21:e1012873 (2025)

Associated data/code:           
PDBe: 8r6x
EMDB: EMD-18968

Snapshots of Pseudomonas aeruginosa SOS response activation complex reveal structural prerequisites for LexA engagement and cleavage

Vascon F^†, De Felice S^†, Gasparotto M, Huber S, Catalano C, Chinellato M, Grinzato A, Filipini F, Maso M, Jakobi AJ, Cendron L

iScience 28:111726 (2025)

Associated data/code:       
PDBe: 8b0v, 8s70, 8s7g
EMDB: EMD-19761, EMD-19771

Structural basis of antimicrobial membrane coat assembly by human GBP1

Kuhm T, Taisne CM, de Agrela Pinto C, Gross L, Giannopolou EA, Huber ST, Pardon E, Steyaert J, Tans S, Jakobi AJ

Nature Structural & Molecular Biology 32:172–184 (2025)

Associated data/code:           
PDBe: 8cqb
EMDB: EMD-16813, EMD-16814, EMD-16815, EMD-16794
Featured as NSMB Research Briefing.

The guanylate-binding protein GBP1 forms a protein coat that enwraps cytosol-invasive bacteria

Jakobi AJ

Nature Structural & Molecular Biology 32:8–9 (2025)

Associated data/code:         


Research Briefing associated with Kuhm et al.:Structural basis of antimicrobial membrane coat assembly by human GBP1.

Roodmus: A toolkit for benchmarking heterogeneous electron cryo-microscopy reconstructions

Joosten M^†, Greer J^†, Parkhurst J, Burnley T^#, Jakobi AJ^#

IUCrJ 11:951-965 (2024)

Associated data/code:       


Roodmus is a Python-based toolkit to generate synthetic cryo-EM datasets of continous molecular heterogeneity by sourcing conformational variability from molecular dynamics simulations. Its development was a joint effort with Joel Greer and Tom Burnley at CCPEM.

Femtolitre volume manipulation for cryo-EM sample preparation of subcellular extracts

Shastri V^†, Pronk J^†, Verlinden E^†, Torres Gonzàles D, Sarajilic E, Laeven P, Evers WH, Frederix P, Staufer U, Jakobi AJ^#, Ghatkesar MK^#

BioRxiv 2024.07.04.602102 (2024)

Associated data/code:       


– this article is a BioRxiv preprint and has not yet been certified by peer review

Structure-based mechanism of riboregulation of the metabolic enzyme SHMT1

Spizzichino S, Di Fonzo F, Marabelli C, Tramonti A, Chaves-Sanjuan A, Parroni A, Boumis G, Romano Liberati F, Paone A, Montemiglio LC, Ardini M, Jakobi AJ, Bharadwaj A, Tartaglia GG, Paiardini A, Contestabile R, Swuec P, Rinaldo S, Bolognesi M, Giardina G, Cutruzzolà F

Molecular Cell 84:2682-2697.e6 (2024)

Associated data/code:       
PDBe: 8r7h, 8a11, 8s7g
EMDB: EMD-18973, EMD-15065

Structural biology of microbial gas vesicles: historical milestones and current knowledge

Huber ST and Jakobi AJ

Biochemical Society Transactions 52:205-215 (2024)

Associated data/code:         


In this review article we review the 60-year journey in quest for a high-resolution structural model of gas vesicles. Stefan’s beautiful illustration was featured on the cover!

Particle fusion of super-resolution data reveals the unit structure of Nup96 in Nuclear Pore Complex

Wang W, Jakobi AJ, Wu Y-L, Ries J, Stallinga S, Rieger B

Scientific Reports 13:13327 (2023)

Associated data/code:           


A publisher correction is associated with this article.

Robust local thickness estimation of sub-micrometer specimen by 4D-STEM

Skoupý R, Boltje DB, Slouf M, Mrázová K, Láznička T, Taisne CM, Krzyzanek, Hoogenboom JP, Jakobi AJ

Small Methods 7:2300258 (2023)

Associated data/code:       

Cryo-EM structure of gas vesicles for buoyancy-controlled motility

Huber ST, Terwiel D, Evers W, Maresca D^#, Jakobi AJ^#

Cell 186:975-986 (2023)

Associated data/code:         
PDBe: 7r1c
EMDB: EMD-14238
Featured as News & Views in Nature Structural & Molecular Biology by Katarzyna Ciazynska.

Multivalent interactions facilitate motor-dependent protein accumulation at growing microtubule plus ends

Maan R, Reese L, Volkov VA, King MR, van der Sluis E, Andrea N, Evers WH, Jakobi AJ, Dogterom M

Nature Cell Biol. 25:975-986 (2023)

Associated data/code:         

EMDB: EMD-14106, EMD-14107, EMD-14108, EMD-14109, EMD-14110, EMD-14110, EMD-14113

Nanofluidic chips for cryo-EM sample preparation from picoliter sample volumes

Huber ST, Sarajilic E, Huijink R, Evers WH, Jakobi AJ

eLife 11:e72629 (2022)

Associated data/code:         
PDB: 7ohf
EMDB: EMD-12901, EMD-12902, EMD-12903, EMD-12914, EMD-12915, EMD-12917

A cryogenic, coincident fluorescence, electron, and ion beam microscope

Boltje DB, Hoogenboom JP, Jakobi AJ, Jensen GJ, Jonker CTH, Kaag MJ, Koster AJ, Last MGF, de Agrela Pinto C, Plitzko JM, Raunser S, Tacke S, Wang Z, van der Wee EB, Wepf R, ten Hoedt S

eLife 11:e82891 (2022)

Associated data/code:         


Highlighted in TU Delft News

Electron scattering properties of biological macromolecules and their use in cryo-EM map sharpening

Bharadwaj A, Jakobi AJ

Faraday Discussions 11:e72629 (2022)

Associated data/code:         
PDBe: 6y5a
EMDB: EMD-10692

Map/model validation and machine learning in EM

Bakker SE, Bergeron J, Bharadwaj A, Bhella D, Bullough P, Chau P-L, Frank RAW, Jakobi AJ, Joseph AP, Kühlbrandt W, Lahiri I, Menday R, Muench SP, Nakasone M, Nerukh D, Paris G, Russo CJ, Saibil HR, Scheres SHW, Sherawat V, Shah AR, Thorn A, Vilas JL, Zanetti G

Faraday Discussion 240:229-242 (2022)

This is a companion article to the above paper containing the public discussion of the paper at the Faraday Discussion “Challenges in biological cryo electron microscopy Faraday Discussion”

Guidelines for the use and interpretation of assays for monitoring autophagy

Klionsky D, Abdel-Aziz AK, Abdelfatah S, Abdoli A, Abel S, …, Jakobi AJ, et.al.

Autophagy 27:1-240 (2021)

Structural basis of p62/SQSTM1 helical filaments and their role in cellular cargo uptake

Jakobi AJ, Huber ST, Mortensen SA, Schultz SW, Palara A, Kuhm T, Shrestha BK, Lamark T, Johansen T, Brech A, Sachse C

Nature Communications 11:440 (2020)

Associated data/code:       
PDB: 6tgn, 6tgp, 6tgs, 6th3, 6tgy
EMDB: EMD-10499, EMD-10500, EMD-10501, EMD-10502,

Seeing with electrons

Arjen J. Jakobi

Europhysics News 51:20-23 (2020)

This short overview article is part of the EPN Special Issue on Physics of Living Matter

Comparing Cryo-EM Reconstructions and Validating Atomic Model Fit using Difference Maps

Joseph AP , Jakobi AJ, Burnley T, Patwardhan A, Topf M, Wynn M.

J Chem In Model 60:2552-2560 (2020)

Associated data/code:       
Source PDBs for analysis: 5cfb, 5vdh, 3jad, 3jaf, 5ni1

Improvement of production and isolation of human neuraminidase-1 in cellulo crystals

Koiwai K, Tsukimoto J, Higashi T, Mafune F, Miyajima K, Nakane T, Matsugaki N, Jakobi AJ, Sugahara M, Tanaka T, Tono K, Joti Y, Yabashi M, Nureki O, Mizohata E, Nakatsu T, Nango E, Iwata S, Chavas LMG, Senda T, Itoh K, Yumoto F

ACS Appl. Biol. Mater. 2:4941-4952 (2019)

Associated data/code:       

Thresholding of cryo-EM density maps by false discovery rate control]

Beckers M, Jakobi AJ, Sachse C

IUCrJ 6:1-16 (2019)

Associated data/code:         


Highlighted in IUCrJ Editorial Notes

Model-based local density sharpening of cryo-EM maps

Jakobi AJ, Wilmanns M, Sachse C

eLife 6:e27131 (2017)

Associated data/code:       
Source PDBs for analysis: 5a1a, 3j5p, 5a63, 5fja, 5afi, 1y7t
Source maps for analysis: EMD-2948, EMD-5778, EMD-3061, EMD-3180, EMD-2847, EMD-6287

Highlighted in IUCrJ Editorial Notes

Structural insights into transcription initiation by yeast RNA polymerase I

Sadian Y, Tafur L, Kosinski J, Jakobi AJ, Wetzel R, Buczak K, Hagen WJH, Beck M, Sachse C, Mueller CW

EMBO J 36:2698-2709 (2017)

Associated data/code:       
PDB: 5oa1
EMDB: EMD-3728, EMD-3728, EMD-3729

Molecular structures of transcribing RNA polymerase I

Tafur L, Sadian Y, Hoffmann NA, Jakobi AJ Wetzel R, Hagen WJH, Sachse C, Muller CW

Molecular Cell 64:2698-2709 (2016)

Associated data/code:       
PDB: 5m5w, 5m64, 5m5x, 5m5y
EMDB: EMD-3446, EMD-3447, EMD-3448, EMD-3449

An atomic model of the HIV-1 capsid-SP1 layer reveals structures regulating assembly and maturation

Schur FKM, Obr M, Wan W, Jakobi AJ, Sachse C, Krausslich HG, Briggs JAG

Science 353:506-508 (2016)

Associated data/code:         
PDB: 5l93
EMDB: EMD-4015

Characterization of Atg38 and NRBF2, a fifth subunit of the autophagic Vps34 complex

Ohashi Y, Soler N, Garcia Ortegon M, Zhang L, Kirsten M, Perisic O, Masson, GR, Burke J, Jakobi AJ, Apostolakis AA, Johnson CM, Ohashi M, Ktistakis NT, Sachse C, Williams RL

Autophagy 12:2129-2144 (2016)

Associated data/code:       
PDB: 5kc1, 5kc2
EMDB: EMD-8235

Higher-order assemblies of oligomeric cargo receptor complexes form the membrane scaffold of the Cvt vesicle

Bertipaglia C, Jakobi AJ, Tarafder AK, Bykov YS, Picco A, Kukulski W, Kosinski J, Hagen WJH, Wilmanns M, Kaksonen M, Briggs JAG, Sachse C

EMBO Reports 17:1044-1060 (2016)

Associated data/code:       
PDB: 5jm0, 5jm6
EMDB: EMD-8166
Featured in EMBOpress Collection on Autophagy and highlighted in EMBL News

Transcribing RNA polymerase III observed by electron cryo-microscopy

Hoffmann NA, Jakobi AJ, Vorlander MK, Sachse C, Muller CW

FEBS J 283:2811-19 (2016)

In cellulo X-ray Diffraction of Native Alcohol Oxidase Crystals in Yeast Cells by Serial Femtosecond Crystallography

Jakobi AJ^#, Passon DM, Knoops K, Stellato F, White TA, Seine T, Messerschmidt M, Chapman HN, Wilmanns M

IUCrJ 3:88-95 (2016)

Associated data/code:       


Highlighted in IUCrJ Editorial Notes, DESY Photon Science Highlights, DESY News, Femto, Research in Germany, CUI, chemie.de

Molecular structures of unbound and transcribing RNA polymerase III

Hoffmann NA^*<, Jakobi AJ^*<, Morcillo-Moreno M, Glatt S, Sachse C, Mueller CW

Nature 528:231-236 (2015)

Associated data/code:       
PDB: 5fj8, 5fj9, 5fja
EMDB: EMD-3178, EMD-3179, EMD-3180

Highlighted in EMBL News

An organized co-assembly of clathrin adaptors is essential for endocytosis

Skruzny M, Desfosses A, Prinz S, Dodonova S, Uetrecht C, Gieras A, Jakobi AJ, Abella M, Hagen WJH, Schulz J, Meijers R, Rybin V, Briggs JAG, Sachse C, Kaksonen M

Developmental Cell 33:150-162 (2015)

Associated data/code:       
PDB: 5ahv
EMDB: EMD-2896, EMDB: EMD-2897
Highlighted in EMBL News

Seeing Tobacco Mosaic Virus through direct electron detectors

Fromm SA, Bharat T, Jakobi AJ, Hagen W, Sachse C

J Struct Biol 189:87-89 (2015)

Associated data/code:         
PDB: 4udv
EMDB: EMD-2833, EMD-2834, EMD-2835, EMD-2836, EMD-2837, EMD-2838, EMD-2839, EMD-2840, EMD-2841, EMD-2842

Characterization of the mycobacterial Acyl-CoA carboxylase holo complexes reveals their functional expansion into amino acid catabolism

Ehebauer MT, Jakobi AJ, Noens EE, Laubitz D, Cichocki B, Marrakchi H, Laneelle MA, Daffe M, Sachse C, Dziembowski A, Sauer U, Wilmanns M

PLoS Pathogens 11:e1004623 (2015)

Associated data/code:       

Novel Sequence Variation affects GPIba in Post-diarrheal Hemolytic Uremic Syndrome

Volokhina E, Jakobi AJ, Urbanus RT, Huizinga EG, Sluiter H, Dineke Westra D, van Heerde W, van de Kar N, van den Heuvel L

J Nephrol Therapeutic S11:007 (2014)

The guanine nucleotide exchange factor Rlf interacts with SH3 domain-containing proteins via a binding site with a preselected conformation

Popovic M^*<, Jakobi AJ^*<, Rensen-de Leeuw M, Rehmann H

J Struct Biol 183:312-319 (2013)

Associated data/code:       
PDB: 4jgw

Calcium modulates force sensing by the von Willebrand Factor A2 domain

Jakobi AJ, Mashaghi A, Tans S, Huizinga EG

Nature Communications 2:e385 (2012)

Associated data/code:       
PDB: 3zqk

Featured in: Chemisch Weekblad C2W, NWO, AMOLF, NU.nl

A rapid cloning method employing orthogonal end protection

Jakobi AJ, Huizinga EG

PLoS One 7:e37617 (2012)

Associated data/code:       

An integrated fragment based screening approach for the discovery of small molecule modulators of the VWF-GPIb interaction

Jose RA, Voet A, Broos K, Jakobi AJ, Bruylants G, Egle B, Zhang KY, De Maeyer M, Deckmyn H, De Borggraeve WM

Chem Commun 48:11349-11351 (2012)

Associated data/code:       

Structure of Ammonium 2-aminopyrazine-3-carboxylate

Jakobi AJ, Lutz M

Acta Cryst Section E 67:o984 (2011)

Associated data/code:       
CIF: CCDC-820283

ParaFrag - a novel approach for surface-based similarity comparison of molecular fragments

Jakobi AJ, Mauser H, Clark T

J Mol Model 14:547-558 (2008)

Associated data/code: