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Mucosa-associated lymphoid tissue protein 1 (MALT1) plays a key role in adaptive immune responses by modulating specific intracellular signalling pathways that control the development and proliferation of both T and B cells. Dysfunction of these pathways is coupled to the progress of highly aggressive lymphoma as well as to potential development of an array of different immune disorders. In contrast to other signalling mediators, MALT1 is not only activated through the formation of the CBM complex together with the proteins CARMA1 and Bcl10, but also by acting as a protease that cleaves multiple substrates to 1 13 promote lymphocyte proliferation and survival via the NF-κB signalling pathway. Herein, we present the partial H, C Ile/ Val/Leu-Methyl resonance assignment of the monomeric apo form of the paracaspase-IgL domain of human MALT1. Our results provide a solid ground for future elucidation of both the three-dimensional structure and the dynamics of MALT1, key for adequate development of inhibitors, and a thorough molecular understanding of its function(s). 1 13 Keywords MALT1 · Paracaspase · H · C Ile · Val · Leu-Methyl resonance Introduction proliferation of T and B cells (Ruland et al. 2003; Ruefli- Brasse et al. 2003; Jaworski et al. 2014; Gewies et al. 2014; MALT1 has been identified as a key player in intracellular Bornancin et al. 2015; Juilland and Thome 2018; Schlau- pathways that lead to the activation of the transcription fac- derer et al. 2018; Gehring et al. 2018; Hailfinger et al. 2009; tor NF-κB which ultimately controls the development and Dunleavy and Wilson 2014; Lenz, 2015; Uren et al. 2000). The function of MALT1 is triggered upon activation of B- or T-cell receptors, as well as NK cells through interactions Xiao Han and Maria Levkovets author have contributed equally to this work. with Fc receptors (Rosebeck et al. 2011). Dysfunctions in these MALT1-directed pathways are coupled to the potential * Peter Agback development of aggressive lymphomas with high resistance email@example.com to current chemotherapies, as well as to the initiation of an * Vladislav Yu. Orekhov array of immune disorders (Solsona et al. 2022) Full length firstname.lastname@example.org MALT1 is composed of five domains (Hailfinger et al. 2009) including the N-terminal death domain (DD), two immuno- Science for Life Laboratory, Department of Medicine, Karolinska Institute, and, Division of Infectious Diseases, globulin-like domains (IgL and IgL ), the paracaspase or 1 2 Karolinska University Hospital, 171 76 Stockholm, Sweden caspase-like domain (Casp) and a third immunoglobulin- Department of Chemistry and Molecular Biology, University like domain (IgL ), followed by an unstructured C-terminal of Gothenburg, Box 465, 40530 Gothenburg, Sweden tail domain (Fig. 1A). The triggering of activating receptors Department of Structural Biology, Shemyakin-Ovchinnikov, from both innate and adaptive immune responses induces Institute of Bioorganic Chemistry RAS, Moscow, the formation of CARMA-BCL10-MALT1 (CBM) com- Russia 117997 plexes (Ruland and Hartjes 2019). Indeed, CBM formation Department of Molecular Sciences, Swedish University is pivotal for the adequate activation of the NF-κB transcrip- of Agricultural Sciences, Box 7015, 750 07 Uppsala, Sweden tion factor. The DD domain of MALT1 binds to the core of Swedish NMR Centre, University of Gothenburg, Box 465, the BCL10 filament through interactions with the caspase 40530 Gothenburg, Sweden Vol.:(0123456789) 1 3 364 X. Han et al. Fig. 1 Domain organization. A Schematic representation of the oli- folding unit that was used within the present study. C Sequence and gomer complex formed by MALT1 and BCL10. MALT1 comprises numbering of human MALT1(Casp-IgL ) domains in which the 3 338–719 five domains including the N-terminal DEATH domain (DD), two IgL domain is highlighted and typed in italic. The C-terminal his- immunoglobulin-like domains (IgL and IgL ), the caspase-like tag is also depicted. The amino acids Ile, Leu and Val are labelled in 1 2 domain (Casp) and a third immunoglobulin-like domain (IgL ) B blue, bold black and red, respectively Schematic representation of the MALT1(Casp-IgL ) self- 3 338–719 activation and recruitment domain (CARD) of BCL10 More recent data suggested that ubiquitination of the IgL (Schlauderer et al. 2018), while additional interactions are domain may induce conformational changes that could be also formed between the IgL and IgL domains of MALT1 allosterically communicated to the active site of the paracas- 1 2 and the Ser/Thr rich domain of BCL10 (Langel et al. 2008) pase domain of MALT1 (Schairer et al. 2020). (Fig. 1A). It should be noted that the C-terminal section Crystal structures of individual MALT1 domains and of MALT1, which comprises the paracaspase and the IgL combinations thereof in complex with allosteric ligands have domains, is most probably protruding out from the BCL10 been previously determined (Yu et al. 2011; Eitelhuber et al. filament, although its structure could not be detected due to 2015; Schlauderer et al. 2013). Furthermore, the recently high flexibility (Schlauderer et al. 2018) Thus, the molecular developed AlfaFold prediction server provides an excellent and dynamic bases underlying the potential allosteric modu- source of reliably predicted three-dimensional structures of lation of the function of this section of MALT1 remain in proteins and protein domains (Jumper et al. 2021), including our opinion unknown. human full-length MALT1 in monomeric form. However, Importantly, it has been demonstrated that the regulating although crystal structures provide crucial atomic-scale function of MALT1 on NF-κB can be exerted by at least two information about the three-dimensional fold of proteins as routes, one of which includes the protease activity acquired well as exquisite architectural details of e.g. catalytic sites, by MALT1 upon participating in the formation of the CBM they still represent snapshots of energy minimized states and complex (Che et al. 2004; Solsona et al. 2022; Rebeaud et al. can thus seldom provide adequate information for e.g. estab- 2008; Coornaert et al. 2008). However, it should be noted lishing the dynamic bases underlying allosteric communica- that MALT1 promotes a second route for NF-κB activation tion. Noteworthy, to the best of our knowledge, the three- by acting as a scaffold when bound to BCL10, recruiting dimensional structure of the apo monomeric form of the E3 ubiquitin ligases, such as TRAF6 and the linear ubiq- human MALT1(Casp-IgL ) in solution has remained 3 338–719 uitin chain assembly complex (LUBAC), which ultimately missing and all available crystal structures of MALT1 are results in ubiquitination of BCL10 and MALT1 (Sun et al. dimer (Yu et al. 2011; Wiesmann et al. 2012). In contrast, 2004; Yang et al. 2014; Deng et al. 2000; Oeckinghaus et al. NMR spectroscopy can provide much more ample informa- 2007). It has been previously demonstrated that activation of tion about both domain and local conformational flexibili - MALT1 requires the monoubiquitination of residue K644 on ties. It has been previously demonstrated that the truncated the surface of the IgL domain (Fig. 1A) (Pelzer et al. 2013). version of MALT1 which comprises only the caspase-like 1 3 Assignment of IVL‑Methyl side chain of the ligand‑free monomeric human MALT1 paracaspase‑IgL … 365 and the IgL domains MALT1(Casp-IgL ) (Fig. 1B, buffer containing 200–500 mM imidazole. A Q-Sepharose 3 3 338–719 C) retains an active fold (Wiesmann et al. 2012) and that HP column (GE Healthcare) was used to separate the mon- it forms dimers that are functionally important (Hachmann omeric MALT1(Casp-IgL ) protein from the dimer 3 338–719 et al. 2012; Wiesmann et al. 2012). Hence, we here focused form. A final size exclusion chromatography (SEC) step our efforts on this part of MALT1. We have previously using a HiLoad 16/600 Superdex 200 prep grade column 15 13 1 reported the almost complete N/ C/ H backbone assign- (GE Healthcare) was performed, with running bue ff r 20 mM ment of the apo form of the human MALT1 paracaspase HEPES 7.4, 50 mM NaCl, 1 mM DTT. The final monomer region together with the third immunoglobulin-like (IgL ) MALT1(Casp-IgL ) protein sample was subsequently 3 3 338–719 domain by high resolution NMR (Unnerstale et al. 2016). exchanged to a buffer (10 mM Tris 7.6, 50 mM NaCl, 2 mM Here, we partially assigned the IVL-Methyl side chains of TCEP, 0.002% NaN3) suitable for NMR experiments using the ligand-free monomeric human MALT1 paracaspase-IgL gravity flow PD10 desalting columns (GE Healthcare). Final domain in solution. yields from a four litres M9 culture were approximately 8 mg of purified protein. Purified monomeric MALT1(Casp- IgL ) -his was concentrated to at least 0.4 mM for 3 338–719 Methods and experiments NMR data acquisition. Expression and purification of labelled MALT1(Casp‑IgL ) NMR spectroscopy 3 338–719 The DNA sequence encoding for the caspase and IgL NMR spectra were recorded at 298 K and 308 K on domains of human MALT1, corresponding to residues 700 MHz (Bruker AVANCE III) or on 800 MHz, 900 MHz 338–719 (Fig. 1C) and a C-terminal His6-tag was cloned (Bruker AVANCE III-HD) spectrometers equipped with into pET21b (Novagen). The MALT1 -his construct cryo-enhanced 5 mm QXI, 3 mm TCI, and 3 mm TCI 338–719 1 15 was transformed into Escherichia coli strain T7 express probes, respectively. 2D H- N Best-TROSY-transverse competent cells and thereafter expressed in different isotopic relaxation optimized spectroscopy (TROSY) was used (Elet- 1 2 15 12 13 labelling combinations in / H, N, / C-labelled M9 sky et al. 2001; Pervushin et al. 1997; Schulte-Herbruggen medium. Chemicals for isotope labelling (ammonium chlo- and Sorensen 2000). Three dimension (3D) Best-TROSY 15 13 ride, N (99%), D-glucose, C (99%), deuterium oxide) type HNCO and 3D HNCA experiments were collected were purchased from Cambridge Isotope Laboratories, Inc. using iterative non-uniformly sampling (NUS) (Favier and Cells were cultivated at 37 ℃ and were induced at an OD Brutscher 2011). Deuterium decoupling was applied in 3D 1 13 of approximately 0.8 for 16 h at 16 ℃ by addition of β-D-1- Best-TROSY HNCA. The assignment of the H, C Methyl thiogalactopyranoside (IPTG) to 0.5 mM final concentration. Val, Leu, Ile amino acids of MALT1(Casp-IgL ) 3 338–719 For the incorporation of methyl groups with the desired was based on a set of 3D resonance experiments including isotopic labelling pattern, alpha-keto acids were added as HMCM(CGCB)CA and HMCM(CGCBCA)CO for Ile/Leu supplements to M9 medium and they served as biosynthetic and HMCM(CB)CA for Val residues. The pulse programs precursors. MALT1(Casp-IgL ) was expressed in 1 were identical to hmcmcbcagpwg3d and hmcmcbcacog- 3 338–719 13 2 L of D O M9 medium using 3 g/L of U-[ C, H]-glucose pwg3d in Bruker TopSpin3.6 except that methyl HMQC (CIL, Andover, MA) as the main carbon source and 1 g/L instead of HSQC and H decoupling were applied (Tuga- of NH Cl (CIL, Andover, MA) as the nitrogen source. One rinov et al. 2014) and 1.8 ms IBurp1 pulse was used for hour prior to induction, precursors were added to the growth selective inversion of CG2 of Ile. medium as previously described (Tugarinov et al. 2006). Intramolecular amide- methyl, NH-CH , interactions For precursors, 70 mg/L alpha-ketobutyric acid, sodium salt were verified through observing cross peaks in 3D SOFAST 13 2 1 15 ( C4, 98%, 3,3- H, 98%) and 120 mg/L alpha-ketoisovaleric (SF), H– N TROSY NOESY experiments. Additional 13 2 acid, sodium salt (1,2,3,4- C4,99%, 3, 4, 4, 4, - H 97%) intramolecular Methyl-Methyl interactions were obtained 13 13 (CIL, Andover, MA) were used. Bacterial growth was con- from 4D C, C-SF HMQC NOESY (Zwahlen et al. 1998) 1 13 13 1 tinued for 16 h at 16 °C and the cells were thereafter har- and 3D H C C H-TOCSY(Kay et al. 1993) experiments. vested by centrifugation. The experimental parameters for acquisition in the Cells were resuspended in lysis buffer 20 mM TrisHCl 2D/3D/4D experiments are summarised in Table 1. (pH7.6), 150 mM NaCl, 2 mM DTT and lysed using ultra- The 3D NUS methyl related experiments were pro- sonicator, followed by centrifugation at 40,000 g for 30 min cessed using NMRpipe (Delaglio et al. 1995) and the IST to remove cell debris. The supernatant was collected and algorithm in the mddnmr software (Kazimierczuk and 2+ incubated with Ni Sepharose 6 Fast Flow (GE Health- Orekhov 2011; Mayzel et al. 2014). The decoupling of care) for 1 h at 4 ℃. The target protein was eluted with lysis 1 3 366 X. Han et al. Table 1 List of acquisition parameters used for NMR experiments Experiments Maximum evolution time, (ms)/ carrier frequency (ppm)/sweep width D1s Scans NUS points NUS % Time (h) (ppm) F3 F2 F1 1 15 a,c 1 15 H- N Best-TROSY 9.4( H)/ 4.7/12 38.9( N)/ 118.0/36.0 – 0.8 4 – – 1.0 1 15 13 3D Best-TROSY- 79.9( H)/ 4.7/16.0 34.3( N)/ 118.0/36.0 19.9( C)/ 173.0/15.0 0.5 16 720 12 6.2 a,f HNCO 1 15 13 3D Best-TROSY – 106.5( H)/ 4.7/12.0 24.0( N)/ 118.0/36.0 42.4( C)/ 54.0/30.0 0.5 16 2400 13.4 32.4 a,b HNCA_2H 1 15 1 15 1 3D H– N SF- 79.9( H)/4.67/16.0 27.4( N)/118/36.0 28.4( H)/4.67/11.0 0.5 16 4600 23 68 NOESY-TROSY 13 13 1 13 1 4D C, C-SF-HMQC F481.0( H)/4.7/14.0 F3/F29.8( C)/ F119.7( H)/4.7/1.8 0.7 8 5400 10.5 84 NOESY-HMQC 17.0/18.0 1 13 13 1 g 1 13 1 H C C H-TOCSY 90.9( H)/4.67/1616.0 4.5( C)/39/80 22.7( H)/4.67/8 1.0 4 – – 40 36.0 11.0 1 13 a,c 1 13 H-C HMQC 94.6( H)/4.7/12.0 22.5( C)17.0/20.0 – 1.0 8 – – 0.5 1 13 13 HMCM(CGCBCA) 91.8( H)/ 4.7/14.0 13.1( C)/16.0/16.0 28.9( C)/ 171.0/11.0 1.0 16 1612 60 37.4 a,b,d,f CO_2H 4.74.7 1 13 13 HMCM(CGCB) 91.8( H)/ 4.7/14.0 13.1( C)/16.0/16.0 31.8( C)/ 39/20.0 1.0 16 1182 22 27 a,b,d CA_2H 4.74.7 a,b,e 1 13 13 HMCM(CB)CA_2H 91.8( H)/ 4.7/14.0 13.1( C)/16.0/16.0 31.8( C)/39.0/20.0 1.0 16 1720 32 38.4 4.74.7 Experiments performed on an 800 MHz spectrometer Experiments performed with deuterium decoupling Experiments on 900 MHz spectrometer Optimized for Ile and Leu Optimized for Val T = 308 K Experiments performed on an 700 MHz spectrometer 13 α 13 β the homonuclear one-bond C - C scalar coupling in Extent of assignments and data deposition the HNCA, HMCM(CB)CA, and the HMCM(CGCB)CA experiments was performed by deconvolution (Kazimierc- Thorough knowledge of both backbone and side chain chem- 1 13 15 zuk et al. 2020). The H, C and N chemical shifts were ical shift nuclei is important for a complete description of the 13 15 referred to DSS- . The C and N chemical shifts were structural features of the human MALT1(Casp-IgL ) d6 3 338–719 15 13 1 referenced indirectly. The backbone chemical shifts of complex. We have previously reported the N/ C/ H 1 15 13 α 13 β 13 MALT1(Casp-IgL ) , HN, N, C , C and C´ backbone assignment of the apo form of MALT1(Casp- 3 338–719 nuclei, have been previously assigned by us (Unnerstale IgL ) in solution (Unnerstale et al. 2016). Methyl- 3 338–719 et al. 2016) using the Target Acquisition approach (Isaks- specific isotope labelling has been recently developed as a son et al. 2013; Jaravine and Orekhov 2006; Jaravine et al. powerful tool to study the structure, dynamics and interac- 2008), and can be found in the Biological Magnetic Reso- tions of large proteins and protein complexes by solution- nance Data Bank (Ulrich et al. 2008) (http://www . bmrb. state NMR (Tugarinov et al. 2006; Rosenzweig and Kay w i s c . e d u /) with the BMRB accession code 25,674. All 2014). Four large hydrophobic clusters assembled by methyl analyses were performed manually in CcpNmr Analysis groups of Ile, Leu, Val amino acids could be distinguished 3.0.4 (Vranken et al. 2005). For visualization of the results in the structure of MALT1(Casp-IgL ) (Fig. 2). The 3 338–719 of Methyl’s assignment on the MALT1(Casp-IgL ) first cluster (I) is located mainly in IgL domain, while the 3 338–719 model the UCSF Chimera package (Pettersen et al. 2004) second cluster (II) is localized between the IgL and Casp was used. The model was created based on the crystal (Fig. 2A). The third (III) and fourth (IV) clusters are struc- structure of MALT1 (PDB ID: 3V55) and adding miss- tural parts of the Casp domain and are located on both side ing loops according to the comparative protein modelling of beta sheets (Fig. 2B). approach(Sali & Blundell 1993). In this study, we focused on the assignment of the methyl resonances for the side chains of valine (Val), leucine (Leu) 1 3 Assignment of IVL‑Methyl side chain of the ligand‑free monomeric human MALT1 paracaspase‑IgL … 367 Fig. 2 Annotation of the Methyl groups assignment in the MALT1. A hydrophobic clusters located around the beta sheets. The methyls of Four large hydrophobic clusters of methyl Ile, Val, Leu are coloured Ile, Val and Leu residues that are lying outside of the hydrophobic by: (I) yellow in IgL domain, (II) violet, between IgL and paracas- cores of MALT1 are coloured in blue. The assigned methyl groups 3 3 pase domains, (III) and (IV) green and red for clusters located on of the amino acids are marked by dark colours corresponding to the both sides of the beta sheets in the paracaspase domain. B 90°-rotated clusters and the unassigned residues are coloured in corresponding projection of the paracaspase domain only showing (III) and (IV) light colours and isoleucine (Ile) amino acid residues in the human of the relatively low sensitivity of the methyl out-and-back MALT1(Casp-IgL ) construct. The assignment of 3D experiments, which lack cross-peaks for a number of 3 338–719 1 13 1 13 the H and C resonances of methyl group in NMR spectra methyl signals observed in 2D H- C HMQC (Fig. 3). The of large proteins remains a challenge. We therefore used a apparent reason for this low sensitivity is fast relaxation of 1 13 combination of two highly efficient and complementing pro- the H and C nuclei involved in the magnetization transfer. tocols. We started with the conventional approach, where In addition, the Casp domain is apparently involved in a the methyl resonances were connected to the known back- slow dynamic process leading to line broadening. The out- bone assignments using methyl out-and-back experiments and-back HMCM(CGCBCA)CO_2H experiment performed (Tugarinov et al. 2014). Then, the methyl assignments were at a higher temperature (308 K) showed higher sensitivity. validated and further expanded using the second approach However, we performed most of the experiments at 298 K, based on Nuclear Oberhausen Effect (NOE) cross-peak data, because MALT1(Casp-IgL ) is unstable at 308 K or 3 338–719 peak residue type classification and a known 3D structure higher temperatures. It should be noted that this type of or a reliable structural model (Rossi et al. 2016; Pritišanac experiment for large proteins usually shows best perfor- et al. 2019; Nerli et al. 2021). mance at high temperature, which therefore limits its appli- cation to temperature-stable proteins. 1 13 Assignment of H, C resonances for methyl Ile, Leu and Val residues in human α 1 13 MALT1(Casp‑IgL ) through Methyl ‑C / Assignment of H, C resonances for methyl 3 338–719 or C′ correlation Ile, Leu and Val residues in human MALT1(Casp‑IgL ) based on NOEs 3 338–719 Our initial approach was based on sets of previously devel- contacts oped experiments (Tugarinov and Kay 2003), where inter- 1 13 actions between H/ C labelled methyl groups of Ile, Val As a next step, we combined backbone amide and side- α 2 13 and Leu residues, and C or C′ nuclei in triple, H, C, chain methyl assigned above with NOEs obtained from 15 1 15 N, labelled MALT1(Casp-IgL ) protein were moni- NH-Methyl NOE in 3D ( H- N) NOESY and Methyl- 3 338–719 13 13 tored. A higher resolution was achieved through NUS acqui- Methyl NOE interactions in 4D C- C NOESY spectrum sition in indirect detection (Table 1). Combination of the (Nerli et al. 2021) versus the available spatial structure of previously obtained backbone assignment (Unnerstale et al. MALT1. Comparison of the observed NOE cross peaks and 2016) and chemical shifts for C and C’ from the out-and- their intensities to the corresponding distances in the crystal back methyl experiments (Table 1) allowed us to assign 10 structure of MALT1(Casp-IgL ) permitted additional 3 338–719 1 13 (out of total 18) Ile, 12/108 Leu and 15 (of 52) Val methyl assignment of the H, C methyl resonances. Pairs of gemi- 13 δ1 13 δ2 13 γ1 13 γ2 groups. The assignment at this stage was incomplete because nal C / C and Val C / C resonances were verified 1 3 368 X. Han et al. 1 13 Fig. 3 Annotated H, C- HMQC spectrum of monomeric human apo-MALT1(Casp- IgL ) Assignments of 3 338–719 the cross peaks are depicted by numbers of the correspond- ing amino acid residues in the protein sequence. Numbers for Ile, Val and Leu are coloured in blue, red and black, respec- tively. The two insets enlarge the most crowded regions of the spectrum through Methyl-Methyl TOCSY interaction (Kay et al. 1993) a total of 98 ILV (61 in Casp and 37 in IgL ) amino acid 1 13 13 1 in H C C H-TOCSY experiment. residues (only 1 methyl for Ile) we assigned 79 (44 for 1 13 Figure 3 depicts the H- C HMQC spectrum with the Casp and 35 for IgL ): 88% of Val (13 in Casp and 10 in methyl assignment of MALT1(Casp-IgL ) Out of IgL , coloured in red in Fig. 3), 100% of Ile (10 in Casp 3 338–719. 3 1 3 Assignment of IVL‑Methyl side chain of the ligand‑free monomeric human MALT1 paracaspase‑IgL … 369 Open Access This article is licensed under a Creative Commons Attri- and 8 in IgL , coloured in blue in Fig. 3) and 70% of Leu bution 4.0 International License, which permits use, sharing, adapta- (21 in Casp and 17 in IgL , coloured in black in Fig. 3). tion, distribution and reproduction in any medium or format, as long The majority of the assigned methyls are located in the as you give appropriate credit to the original author(s) and the source, IgL domain and belong to the hydrophobic clusters I and provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are II. Assignment of the remaining methyls in clusters (III) included in the article’s Creative Commons licence, unless indicated and (IV) was hindered by the incomplete backbone assign- otherwise in a credit line to the material. If material is not included in ment, low sensitivity in the out-an-back spectra, as well as the article’s Creative Commons licence and your intended use is not due to substantial overlap of several methyl signals of Leu permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a residues. The methyl chemical shifts have been added to copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. the Biological Magnetic Resonance Data Bank deposition 25,674. (Ulrich et al, 2008) (http://www .bmrb. wisc. edu/ ). References Bornancin F, Renner F, Touil R, Sic H, Kolb Y, Touil-Allaoui I, Rush Conclusion JS, Smith PA, Bigaud M, Junker-Walker U, Burkhart C, Dawson J, Niwa S, Katopodis A, Nuesslein-Hildesheim B, Weckbecker 1 13 G, Zenke G, Kinzel B, Traggiai E, Brenner D, Brustle A, Paul We present in this study the partial H / C Ile/Leu/Val MS, Zamurovic N, Mccoy KD, Rolink A, Regnier CH, Mak TW, methyl resonance assignments for the apo form of human Ohashi PS, Patel DD, Calzascia T (2015) Deficiency of MALT1 MALT1(Casp-IgL ) . This assignment will play a cru- 3 338–719 paracaspase activity results in unbalanced regulatory and effector t cial role in elucidation of MALT1(Casp-IgL ) struc- and b cell responses leading to multiorgan inflammation. 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Nat Immunol 9(3):263–271. manuscript draft. PA and VO contributed with writing, reviewing and https:// doi. org/ 10. 1038/ ni1561 final editing of the manuscript. TA and PA performed the NMR studies Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax A (1995) on MALT1 stability. VO, DL contributed with NMR measurements and Nmrpipe—a multidimensional spectral processing system based methodology, spectra processing and development for NMR methyl on unix pipes. J Biomol NMR 6(3):277–293. https:// doi. org/ 10. assignment experiments. ML and JW performed assignments using 1007/ Bf001 97809 the ccpn program. PA, TA, TS, AA, and VO conceptualized together Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, the project, supervised different parts of the project and acquired the Pickart C, Chen ZJ (2000) Activation of the IkappaB kinase com- necessary funding acquisition. plex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. 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Biomolecular NMR Assignments – Springer Journals
Published: Oct 1, 2022
Keywords: MALT1; Paracaspase; 1H; 13C Ile; Val; Leu-Methyl resonance
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