Nature Structural &Molecular Biology最新文献_第3页

Non-covalent DNA-protein complex between E. coli YedK and ssDNA containing an abasic site analog 大肠杆菌YedK和含有基本位点类似物的ssDNA之间的非共价dna -蛋白复合物

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2019-06-24 DOI: 10.2210/PDB6NUH/PDB

Petria S. Thompson, K. M. Amidon, Kareem N. Mohni, D. Cortez, B. Eichman

{"title":"Non-covalent DNA-protein complex between E. coli YedK and ssDNA containing an abasic site analog","authors":"Petria S. Thompson, K. M. Amidon, Kareem N. Mohni, D. Cortez, B. Eichman","doi":"10.2210/PDB6NUH/PDB","DOIUrl":"https://doi.org/10.2210/PDB6NUH/PDB","url":null,"abstract":"Abasic (AP) sites are one of the most common DNA lesions that block replicative polymerases. 5-hydroxymethylcytosine binding, embryonic stem cell-specific protein (HMCES) recognizes and processes these lesions in the context of single-stranded DNA (ssDNA). A HMCES DNA-protein cross-link (DPC) intermediate is thought to shield the AP site from endonucleases and error-prone polymerases. The highly evolutionarily conserved SOS-response associated peptidase (SRAP) domain of HMCES and its Escherichia coli ortholog YedK mediate lesion recognition. Here we uncover the basis of AP site protection by SRAP domains from a crystal structure of the YedK DPC. YedK forms a stable thiazolidine linkage between a ring-opened AP site and the α-amino and sulfhydryl substituents of its amino-terminal cysteine residue. The thiazolidine linkage explains the remarkable stability of the HMCES DPC, its resistance to strand cleavage and the proteolysis requirement for resolution. Furthermore, its structure reveals that HMCES has specificity for AP sites in ssDNA at junctions found when replicative polymerases encounter the AP lesion.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"26 1","pages":"613-618"},"PeriodicalIF":16.8,"publicationDate":"2019-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42837871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Human equilibrative nucleoside transporter-1, S-(4-nitrobenzyl)-6-thioinosine bound, merohedrally twinned 人平衡核苷转运体- 1,5 -(4-硝基苄基)-6-硫代氨基糖苷结合，双侧孪生

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2019-06-24 DOI: 10.2210/PDB6OB6/PDB

Nicholas Wright, Seok-Yong Lee

引用次数: 1

Spastin hexamer in complex with substrate Spastin六聚体与底物的复合物

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2019-06-12 DOI: 10.2210/PDB6P07/PDB

C. Sandate, A. Szyk, E. Zehr, G. Lander, A. Roll-Mecak

{"title":"Spastin hexamer in complex with substrate","authors":"C. Sandate, A. Szyk, E. Zehr, G. Lander, A. Roll-Mecak","doi":"10.2210/PDB6P07/PDB","DOIUrl":"https://doi.org/10.2210/PDB6P07/PDB","url":null,"abstract":"The AAA+ ATPase spastin remodels microtubule arrays through severing and its mutation is the most common cause of hereditary spastic paraplegias (HSP). Polyglutamylation of the tubulin C-terminal tail recruits spastin to microtubules and modulates severing activity. Here, we present a ~3.2 A resolution cryo-EM structure of the Drosophila melanogaster spastin hexamer with a polyglutamate peptide bound in its central pore. Two electropositive loops arranged in a double-helical staircase coordinate the substrate sidechains. The structure reveals how concurrent nucleotide and substrate binding organizes the conserved spastin pore loops into an ordered network that is allosterically coupled to oligomerization, and suggests how tubulin tail engagement activates spastin for microtubule disassembly. This allosteric coupling may apply generally in organizing AAA+ protein translocases into their active conformations. We show that this allosteric network is essential for severing and is a hotspot for HSP mutations. AAA+ ATPase spastin recognizes tubulin polyglutamylated C-terminal tails and severs microtubules. A cryo-EM structure of fly spastin with polyGlu reveals how spastin engages with the substrate, an activity allosterically coupled to nucleotide binding and oligomerization.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"26 1","pages":"671-678"},"PeriodicalIF":16.8,"publicationDate":"2019-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47517640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Dimer-of-dimer amyloid fibril structure of glucagon 胰高血糖素的二聚体-二聚体淀粉样纤维结构

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2019-06-05 DOI: 10.2210/PDB6NZN/PDB

Martin D. Gelenter, Katelyn J. Smith, S. Liao, V. Mandala, A. Dregni, M. Lamm, Yu Tian, Wei Xu, D. Pochan, T. Tucker, Yongchao Su, M. Hong

{"title":"Dimer-of-dimer amyloid fibril structure of glucagon","authors":"Martin D. Gelenter, Katelyn J. Smith, S. Liao, V. Mandala, A. Dregni, M. Lamm, Yu Tian, Wei Xu, D. Pochan, T. Tucker, Yongchao Su, M. Hong","doi":"10.2210/PDB6NZN/PDB","DOIUrl":"https://doi.org/10.2210/PDB6NZN/PDB","url":null,"abstract":"Glucagon and insulin maintain blood glucose homeostasis and are used to treat hypoglycemia and hyperglycemia, respectively, in patients with diabetes. Whereas insulin is stable for weeks in its solution formulation, glucagon fibrillizes rapidly at the acidic pH required for solubility and is therefore formulated as a lyophilized powder that is reconstituted in an acidic solution immediately before use. Here we use solid-state NMR to determine the atomic-resolution structure of fibrils of synthetic human glucagon grown at pharmaceutically relevant low pH. Unexpectedly, two sets of chemical shifts are observed, indicating the coexistence of two β-strand conformations. The two conformations have distinct water accessibilities and intermolecular contacts, indicating that they alternate and hydrogen bond in an antiparallel fashion along the fibril axis. Two antiparallel β-sheets assemble with symmetric homodimer cross sections. This amyloid structure is stabilized by numerous aromatic, cation-π, polar and hydrophobic interactions, suggesting mutagenesis approaches to inhibit fibrillization could improve this important drug.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"237 1","pages":"592-598"},"PeriodicalIF":16.8,"publicationDate":"2019-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68202066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Structure of Saccharomyces cerevisiae apo Pan2 pseudoubiquitin hydrolase-RNA exonuclease (UCH-Exo) module 酿酒酵母载子Pan2伪泛素水解酶- rna外切酶(UCH-Exo)模块的结构

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2019-05-22 DOI: 10.2210/PDB6R9I/PDB

T. Tang, J. Stowell, C. Hill, L. Passmore

引用次数: 0

Structure of the human apo TFIIH 人apo TFIIH的结构

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2019-05-20 DOI: 10.2210/PDB6O9M/PDB

Chunli Yan, T. Dodd, Yuan He, J. Tainer, S. Tsutakawa, I. Ivanov

引用次数: 2

Designed repeat protein in complex with Fz7 设计与Fz7复合物的重复蛋白

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2019-05-13 DOI: 10.2210/PDB6NE2/PDB

Luke T. Dang, Y. Miao, A. Ha, K. Yuki, K. Park, C. Y. Janda, K. Jude, K. Mohan, N. Ha, Mario Vallon, Jenny Yuan, J. Vilches-Moure, C. Kuo, K. Garcia, David Baker

{"title":"Designed repeat protein in complex with Fz7","authors":"Luke T. Dang, Y. Miao, A. Ha, K. Yuki, K. Park, C. Y. Janda, K. Jude, K. Mohan, N. Ha, Mario Vallon, Jenny Yuan, J. Vilches-Moure, C. Kuo, K. Garcia, David Baker","doi":"10.2210/PDB6NE2/PDB","DOIUrl":"https://doi.org/10.2210/PDB6NE2/PDB","url":null,"abstract":"To discriminate between closely related members of a protein family that differ at a limited number of spatially distant positions is a challenge for drug discovery. We describe a combined computational design and experimental selection approach for generating binders targeting functional sites with large, shape complementary interfaces to read out subtle sequence differences for subtype-specific antagonism. Repeat proteins are computationally docked against a functionally relevant region of the target protein surface that varies in the different subtypes, and the interface sequences are optimized for affinity and specificity first computationally and then experimentally. We used this approach to generate a series of human Frizzled (Fz) subtype-selective antagonists with extensive shape complementary interaction surfaces considerably larger than those of repeat proteins selected from random libraries. In vivo administration revealed that Wnt-dependent pericentral liver gene expression involves multiple Fz subtypes, while maintenance of the intestinal crypt stem cell compartment involves only a limited subset. Chris Garcia, David Baker and colleagues use a computational approach to develop designed repeat protein binders (DRPBs), which function as human Frizzled (Fz) subtype-selective antagonists and enable identification of Fz subtypes active in different organs.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"26 1","pages":"407-414"},"PeriodicalIF":16.8,"publicationDate":"2019-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44986602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Crystal structure of the PE-bound N-terminal domain of Atg2 Atg2的PE结合N端结构域的晶体结构

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2019-03-20 DOI: 10.2210/PDB6A9J/PDB

T. Osawa, T. Kotani, Tatsuya Kawaoka, Eri Hirata, Kuninori Suzuki, H. Nakatogawa, Y. Ohsumi, N. Noda

{"title":"Crystal structure of the PE-bound N-terminal domain of Atg2","authors":"T. Osawa, T. Kotani, Tatsuya Kawaoka, Eri Hirata, Kuninori Suzuki, H. Nakatogawa, Y. Ohsumi, N. Noda","doi":"10.2210/PDB6A9J/PDB","DOIUrl":"https://doi.org/10.2210/PDB6A9J/PDB","url":null,"abstract":"A key event in autophagy is autophagosome formation, whereby the newly synthesized isolation membrane (IM) expands to form a complete autophagosome using endomembrane-derived lipids. Atg2 physically links the edge of the expanding IM with the endoplasmic reticulum (ER), a role that is essential for autophagosome formation. However, the molecular function of Atg2 during ER–IM contact remains unclear, as does the mechanism of lipid delivery to the IM. Here we show that the conserved amino-terminal region of Schizosaccharomyces pombe Atg2 includes a lipid-transfer-protein-like hydrophobic cavity that accommodates phospholipid acyl chains. Atg2 bridges highly curved liposomes, thereby facilitating efficient phospholipid transfer in vitro, a function that is inhibited by mutations that impair autophagosome formation in vivo. These results suggest that Atg2 acts as a lipid-transfer protein that supplies phospholipids for autophagosome formation. Structural and biochemical data suggest that the essential autophagy protein Atg2 acts as a lipid-transfer protein that supplies phospholipids from the source organelle (especially the ER) to the isolation membranes (IMs) for autophagosome formation.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"26 1","pages":"281-288"},"PeriodicalIF":16.8,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44575561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 31

MukB coiled-coil elbow from E. coli 来自大肠杆菌的MukB盘状弯头

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2019-03-01 DOI: 10.2210/PDB6H2X/PDB

Frank Bürmann, Byung-Gil Lee, Thane Than, Ludwig R. Sinn, Francis J. O’Reilly, S. Yatskevich, Juri Rappsilber, Bin Hu, Kim Nasmyth, Jan Löwe

引用次数: 7

Crystal structure of 5-HT2AR in complex with risperidone 5-HT2AR与利培酮复合物的晶体结构

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2019-02-01 DOI: 10.2210/PDB6A93/PDB

T. K. Kimura, H. Asada, A. Inoue, F. Kadji, D. Im, C. Mori, T. Arakawa, K. Hirata, Y. Nomura, N. Nomura, J. Aoki, S. Iwata, T. Shimamura

{"title":"Crystal structure of 5-HT2AR in complex with risperidone","authors":"T. K. Kimura, H. Asada, A. Inoue, F. Kadji, D. Im, C. Mori, T. Arakawa, K. Hirata, Y. Nomura, N. Nomura, J. Aoki, S. Iwata, T. Shimamura","doi":"10.2210/PDB6A93/PDB","DOIUrl":"https://doi.org/10.2210/PDB6A93/PDB","url":null,"abstract":"Many drugs target the serotonin 2A receptor (5-HT2AR), including second-generation antipsychotics that also target the dopamine D2 receptor (D2R). These drugs often produce severe side effects due to non-selective binding to other aminergic receptors. Here, we report the structures of human 5-HT2AR in complex with the second-generation antipsychotics risperidone and zotepine. These antipsychotics effectively stabilize the inactive conformation by forming direct contacts with the residues at the bottom of the ligand-binding pocket, the movements of which are important for receptor activation. 5-HT2AR is structurally similar to 5-HT2CR but possesses a unique side-extended cavity near the orthosteric binding site. A docking study and mutagenic studies suggest that a highly 5-HT2AR-selective antagonist binds the side-extended cavity. The conformation of the ligand-binding pocket in 5-HT2AR significantly differs around extracellular loops 1 and 2 from that in D2R. These findings are beneficial for the rational design of safer antipsychotics and 5-HT2AR-selective drugs.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"26 1","pages":"121-128"},"PeriodicalIF":16.8,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48866526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 32