Jon Agirre

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• Royal Society University Research Fellow
• Professor (Assistant) at University of York

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. T...

Owing to the difficulties associated with working with carbohydrates, validating glycan 3D structures prior to deposition into the Protein Data Bank has become a staple of the structure-solution pipeline. The Privateer software provides integrative methods for the validation, analysis, refinement and graphical representation of 3D atomic structures...

Proteins frequently undergo covalent modification at the post-translational level, which involves the covalent attachment of chemical groups onto amino acids. This can entail the singular or multiple addition of small groups, such as phosphorylation; long-chain modifications, such as glycosylation; small proteins, such as ubiquitination; as well as...

Nucleic acid electron density interpretation after phasing by molecular replacement or other methods remains a difficult problem for computer programs to deal with. Programs tend to rely on time-consuming and computationally exhaustive searches to recognise characteristic features. We present NucleoFind, a deep-learning-based approach to interpreti...

Tryptophan mannosylation, the covalent addition of an α‐ᴅ‐mannose sugar to a tryptophan side chain, is a post‐translational modification (PTM) that can affect protein stability, folding, and interactions. Compared to other forms of protein glycosylation, it is relatively uncommon but is affected by conformational anomalies and modeling errors simil...

The Section Editors welcome and introduce three new Co-editors to the journal and summarize their expertise in computational structural biology, experimental structural biology and cryo-electron microscopy.

Dynamic changes in protein glycosylation impact human health and disease progression. However, current resources that capture disease and phenotype information focus primarily on the macromolecules within the central dogma of molecular biology (DNA, RNA, proteins). To gain a better understanding of organisms, there is a need to capture the function...

The Acta Cryst. F - Structural Biology Communications Editors explain how important international collaborations are in science and structural biology.

To find out what lies behind the articles published in Acta Cryst. F – Structural Biology Communications the journal now publishes interviews with its authors.

The remediation of the carbohydrate data of the Protein Data Bank (PDB) has brought numerous enhancements to the findability and interpretability of deposited glycan structures, yet crucial quality indicators are either missing or hard to find on the PDB pages. Without a way to access wider glycochemical context, problematic structures may be taken...

The remediation of the carbohydrate data of the Protein Data Bank (PDB) has brought numerous enhancements to the findability and interpretability of deposited glycan structures, yet crucial quality indicators are either missing or hard to find on the PDB pages. Without a way to access wider glyco-chemical context, problematic structures may be take...

The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial and peroxisomal fission, but the regulatory mechanisms remain ambiguous. Here we find that a conserved, intrinsically disordered, six-residue Short Linear Motif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1...

The article by Moorefield et al. [(2023), Acta Cryst. F79, 257–266] demonstrates how structural genomics depositions can be used in undergraduate teaching.

The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial fission, but the regulatory mechanisms remain ambiguous. Here we found that a conserved, intrinsically disordered, six-residue S hort Li near M otif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1 structure an...

The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial fission, but the regulatory mechanisms remain ambiguous. Here we found that a conserved, intrinsically disordered, six-residue S hort Li near M otif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1 structure an...

The oligosaccharides in N-glycosylation provide key structural and functional contributions to a glycoprotein. These contributions are dependent on the composition and overall conformation of the glycans. The Privateer software allows structural biologists to evaluate and improve the atomic structures of carbohydrates, including N-glycans; this sof...

Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. Cancer cells often hijack these mechanisms to disseminate. Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein co...

An introduction to the Proceedings of the 2020 CCP4 Study Weekend on model building which are available as a virtual issue at https://journals.iucr.org/special_issues/2020/CCP42020/.

Nowadays, progress in the determination of three-dimensional macromolecular structures from diffraction images is achieved partly at the cost of increasing data volumes. This is due to the deployment of modern high-speed, high-resolution detectors, the increased complexity and variety of crystallographic software, the use of extensive databases and...

Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. Cancer cells often hijack these mechanisms to disseminate. Here we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein com...

Accurate but protein-only AlphaFold models may show structural fingerprints of likely posttranslational modifications (PTMs). In this issue of PLOS Biology, Bludau and colleagues add a functional context to models by combining them with readily available proteomics results.

Restraint dictionaries are used during macromolecular structure refinement to encapsulate intramolecular connectivity and geometric information. These dictionaries allow previously determined ‘ideal’ values of features such as bond lengths, angles and torsions to be used as restraint targets. During refinement, restraints influence the model to ado...

Phototrophic Gemmatimonadetes evolved the ability to use solar energy following horizontal transfer of photosynthesis-related genes from an ancient phototrophic proteobacterium. The electron cryo-microscopy structure of the Gemmatimonas phototrophica photosystem at 2.4 Å reveals a unique, double-ring complex. Two unique membrane-extrinsic polypepti...

Macromolecular restrained refinement is nowadays the most used method for improving the agreement between an atomic structural model and experimental data. Restraint dictionaries, a key tool behind the success of the method, allow fine-tuning geometric properties such as distances and angles between atoms beyond simplistic expectations. Dictionary...

Iris validation is a Python package created to represent comprehensive per‐residue validation metrics for entire protein chains in a compact, readable and interactive view. These metrics can either be calculated by Iris, or by a third‐party program such as MolProbity. We show that those parts of a protein model requiring attention may generate ripp...

The heterogeneity, mobility and complexity of glycans in glycoproteins have been, and currently remain, significant challenges in structural biology. These aspects present unique problems to the two most prolific techniques: X-ray crystallography and cryo-electron microscopy. At the same time, advances in mass spectrometry have made it possible to...

The heterogeneity, mobility and complexity of glycans in glycoproteins have been, and currently remain, significant challenges in structural biology. Those aspects present unique problems to the two most prolific techniques: X-ray crystallography and cryo-electron microscopy. At the same time, advances in mass spectrometry have made it possible to...

The methodology underpinning the construction, refinement, validation and analysis of atomic models of glycoproteins and protein-carbohydrate complexes has received a long-overdue boost in the last five years. This is a very timely development, as the resolution revolution in electron cryo-microscopy is now routinely delivering structures of key gl...

Alginate is a polymer containing two uronic acid epimers, β-d-mannuronate (M) and α-l-guluronate (G), and is a major component of brown seaweed that is depolymerized by alginate lyases. These enzymes have diverse specificity, cleaving the chain with endo- or exotype activity and with differential selectivity for the sequence of M or G at the cleava...

The methodology underpinning the construction, refinement, validation and analysis of atomic models of glycoproteins and protein-carbohydrate complexes has received a long-overdue boost in the last five years. This is a very timely development, as the resolution revolution in electron cryo-microscopy is now routinely delivering structures of key gl...

α-Amylases are glycoside hydrolases that break the α-1,4 bonds in starch and related glycans. The degradation of starch is rendered difficult by the presence of varying degrees of α-1,6 branch points and their possible accommodation within the active centre of α-amylase enzymes. Given the myriad industrial uses for starch and thus also for α-amylas...

An introduction to the Acta Cryst. F special issue on glycoproteins and protein–carbohydrate complexes in which the contents, the current state of the field and the future of glycan structural biology are briefly discussed.

PDF version of the Keynote file I had uploaded as main file

These are the slides I used as a guide for the Lunchtime Bytes I gave at the CCP4 Study Weekend.

Refinement is a critical step in the determination of a model which explains the crystallographic observations and thus best accounts for the missing phase components. The scattering density is usually described in terms of atomic parameters; however, in macromolecular crystallography the resolution of the data is generally insufficient to determin...

The CCP4 (Collaborative Computational Project, Number 4) software suite for macromolecular structure determination by X-ray crystallography groups brings together many programs and libraries that, by means of well established conventions, interoperate effectively without adhering to strict design guidelines. Because of this inherent flexibility, us...

Scripting programming languages provide the fastest means of prototyping complex functionality. Those with a syntax and grammar resembling human language also greatly enhance the maintainability of the produced source code. Furthermore, the combination of a powerful, machine-independent scripting language with binary libraries tailored for each com...

A brief overview is provided of the history of collaborative computational crystallography, with an emphasis on the Collaborative Computational Project No. 4 (CCP4). The key steps in its development are outlined, with consideration also given to the underlying reasons which contributed, and ultimately led to, the unprecedented success of this ventu...

With the introduction of intuitive graphical software, structural biologists who are not experts in crystallography are now able to build complete protein or nucleic acid models rapidly. In contrast, carbohydrates are in a wholly different situation: scant automation exists, with manual building attempts being sometimes toppled by incorrect diction...

Sugars are the most stereochemically intricate family of biomolecules and present substantial challenges to anyone trying to understand their nomenclature, reactions or branched structures. Current crystallographic programs provide an abstraction layer allowing inexpert structural biologists to build complete protein or nucleic acid model component...

The close-range interactions provided by covalently linked glycans are essential for the correct folding of glycoproteins and also play a pivotal role in recognition processes. Being able to visualise protein–glycan and glycan–glycan contacts in a clear way is thus of great importance for the understanding of these biological processes. In structur...

ADP-glucose pyrophosphorylase (AGPase) catalyzes the rate-limiting step of bacterial glycogen and plant starch biosynthesis, the most common carbon storage polysaccharides in nature. A major challenge is to understand how AGPase activity is regulated by metabolites in the energetic flux within the cell. Here we report crystal structures of the homo...

The industrial conversion of cellulosic plant biomass into useful products such as biofuels is a major societal goal. These technologies harness diverse plant degrading enzymes, classical exo- and endo-acting cellulases and, increasingly, cellulose-active lytic polysaccharide monooxygenases, to deconstruct the recalcitrant β-d-linked polysaccharide...

A cationic class III peroxidase from Sorghum bicolor was purified to homogeneity. The enzyme contains a high-spin heme, as evidenced by UV–visible spectroscopy and EPR. Steady state oxidation of guaiacol was demonstrated and the enzyme was shown to have higher activity in the presence of calcium ions. A FeIII/FeII reduction potential of −266 mV vs...

Protein-carbohydrate interactions play pivotal roles in health and disease. However, defining and manipulating these interactions has been hindered by an incomplete understanding of the underlying fundamental forces. To elucidate common and discriminating features in carbohydrate recognition, we have analyzed quantitatively X-ray crystal structures...

Privateer (http://www.ccp4.ac.uk/html/privateer.html) is a new software package aimed at the detection and prevention of conformational, regiochemical and stereochemical anomalies in cyclic monosaccharide structures. Carbohydrates, including O- and N-glycans attached to protein and lipid structures, are increasingly being studied in cellular biolo...

Despite the key implications carbohydrates have in a multitude of pathological processes, a large number of the sugar-containing structures deposited into the Protein Data Bank (PDB) show nomenclature errors [1] that persist even after the remediation of the PDB archive [2]. Here we present the results from a systematic study of the conformation an...

Triatoma virus (TrV) is a small, non-enveloped virus that has a þssRNA genome and is currently classified under the Cripavirus genus of the Dicistroviridae family. TrV infects haematophagous triatomine insects (Hemiptera: Reduviidae), which are vectors of American trypanosomosis (Chagas disease). TrV can be transmitted through the horizontal faecal...

The interaction between a viral capsid and its genome governs crucial steps in the life cycle of a virus, such as assembly and genome uncoating. Tuning cargo-capsid interactions is also essential for successful design and cargo delivery in engineered viral systems. Here we investigate the interplay between cargo and capsid for the picorna-like Tria...

The members of the Dicistroviridae family are non-enveloped positive-sense single-stranded RNA (+ssRNA) viruses pathogenic to beneficial arthropods as well as insect pests of medical importance. Triatoma virus (TrV), a member of this family, infects several species of triatomine insects (popularly named kissing bugs), which are vectors for human tr...

Background Dicistroviridae is a new family of small, non-enveloped, +ssRNA viruses pathogenic to both beneficial arthropods and insect pests. Little is known about the dicistrovirus replication mechanism or gene function, and any knowledge on these subjects comes mainly from comparisons with mammalian viruses from the Picornaviridae family. Due to...

Statistical analysis (ANOVA, with Microsoft Excel®) between the two groups of mice inoculated with the same concentration of RNA-full TrV capsids and empty TrV particles respectively (3 μg). Considering that the data is normally distributed, this test helped to identify differences between mice inoculated with TrV and mice inoculated with the same...

Here, we describe a goniometer holder to mount standard 96-well crystallization plates directly onto the goniometer head of an oscillation camera. This attachment was designed to check crystallization conditions straight from the crystallization plates under X-rays, and was proven to be useful for checking small crystals and solutions that destabil...

Triatoma Virus (TrV) is a member of the insect virus family Dicistroviridae and consists of a small, non-enveloped capsid that encloses its +ssRNA genome. Using cryo-TEM and 3D reconstruction techniques combined with the fitting of the available crystallographic models, we analyzed the capsids corresponding to mature and several RNA-empty TrV parti...

Dicistroviridae is a new family of small, nonenveloped, and +ssRNA viruses pathogenic to both beneficial arthropods and insect pests as well. Triatoma virus (TrV), a dicistrovirus, is a pathogen of Triatoma infestans (Hemiptera: Reduviidae), one of the main vectors of Chagas disease. In this work, we report a single-step method to identify TrV, a d...

Triatoma virus (TrV) is a non-enveloped +ssRNA virus belonging to the insect virus family Dicistroviridae. Mass spectrometry (MS) and gel electrophoresis were used to detect the previously elusive capsid protein VP4. Its cleavage sites were established by sequencing the N-terminus of the protein precursor and MS, and its stoichiometry with respect...

alpha-Haemolysin (HlyA) is a toxin secreted by pathogenic Escherichia coli, whose lytic activity requires submillimolar Ca(2+) concentrations. Previous studies have shown that Ca(2+) binds within the Asp and Gly rich C-terminal nonapeptide repeat domain (NRD) in HlyA. The presence of the NRD puts HlyA in the RTX (Repeats in Toxin) family of protein...

Here, we describe a goniometer holder to mount standard 96-well crystallization plates directly onto the goniometer head of an oscillation camera. This attachment was designed to check crystallization conditions straight from the crystallization plates under X-rays, and was proven to be useful for checking small crystals and solutions that destabil...

The chaperonin GroEL adopts a double-ring structure with various modes of allosteric communication. The simultaneous positive intra-ring and negative inter-ring co-operativities alternate the functionality of the folding cavities in both protein rings. Negative inter-ring co-operativity is maintained through different inter-ring interactions, inclu...