scholarly journals Single Amino Acid Mutations in the Potato Immune Receptor R3a Expand Response to Phytophthora Effectors

2014 ◽  
Vol 27 (7) ◽  
pp. 624-637 ◽  
Author(s):  
María Eugenia Segretin ◽  
Marina Pais ◽  
Marina Franceschetti ◽  
Angela Chaparro-Garcia ◽  
Jorunn I. B. Bos ◽  
...  
Keyword(s):  
Amino Acid ◽  
Random Mutagenesis ◽  
Nucleotide Binding ◽  
Binding Pocket ◽  
Single Amino Acid ◽  
Effector Protein ◽  
Immune Receptor ◽  
Pathogen Effector ◽  
Oomycete Pathogen ◽  
Amino Acid Mutations

Both plants and animals rely on nucleotide-binding domain and leucine-rich repeat-containing (NB-LRR or NLR) proteins to respond to invading pathogens and activate immune responses. How plant NB-LRR proteins respond to pathogens is poorly understood. We undertook a gain-of-function random mutagenesis screen of the potato NB-LRR immune receptor R3a to study how this protein responds to the effector protein AVR3a from the oomycete pathogen Phytophthora infestans. R3a response can be extended to the stealthy AVR3aEM isoform of the effector while retaining recognition of AVR3aKI. Each one of eight single amino acid mutations is sufficient to expand the R3a response to AVR3aEM and other AVR3a variants. These mutations occur across the R3a protein, from the N terminus to different regions of the LRR domain. Further characterization of these R3a mutants revealed that at least one of them was sensitized, exhibiting a stronger response than the wild-type R3a protein to AVR3aKI. Remarkably, the N336Y mutation, near the R3a nucleotide-binding pocket, conferred response to the effector protein PcAVR3a4 from the vegetable pathogen P. capsici. This work contributes to understanding how NB-LRR receptor specificity can be modulated. Together with knowledge of pathogen effector diversity, this strategy can be exploited to develop synthetic immune receptors.

scholarly journals Mutations within the P2 Domain of Norovirus Capsid Affect Binding to Human Histo-Blood Group Antigens: Evidence for a Binding Pocket

2003 ◽  
Vol 77 (23) ◽  
pp. 12562-12571 ◽  
Author(s):  
Ming Tan ◽  
Pengwei Huang ◽  
Jaroslaw Meller ◽  
Weiming Zhong ◽  
Tibor Farkas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Blood Group ◽  
Binding Pocket ◽  
Single Amino Acid ◽  
Blood Group Antigens ◽  
Sequence Alignments ◽  
Amino Acid Mutation ◽  
Multiple Sequence ◽  
Amino Acid Mutations ◽  
Function Relationship

ABSTRACT Noroviruses (NORs) are an important cause of acute gastroenteritis. Recent studies of NOR receptors showed that different NORs bind to different histo-blood group antigens (HBGAs), and at least four distinct binding patterns were observed. To determine the structure-function relationship for NORs and their receptors, two strains representing two of the four binding patterns were studied. Strain VA387 binds to HBGAs of A, B, and O secretors, whereas strain MOH binds to HBGAs of A and B secretors only. Using multiple sequence alignments, homology modeling, and structural analysis of NOR capsids, we identified a plausible “pocket” in the P2 domain that may be responsible for binding to HBGA receptors. This pocket consists of a conserved RGD/K motif surrounded by three strain-specific hot spots (N302, T337, and Q375 for VA387 and N302, N338, and E378 for MOH). Subsequent mutagenesis experiments demonstrated that all four sites played important roles in binding. A single amino acid mutation at T337 (to A) in VA387 or a double amino acid mutation at RN338 (to TT) in MOH abolished binding completely. Change of the entire RGD motif to SAS abolished binding in case of VA387, whereas single amino acid mutations in that motif did not have an apparent effect on binding to A and B antigens but decreased binding to H antigen. Multiple mutations at the RGK motif of MOH (SIRGK to TFRGD) completely knocked out the binding. Mutation of N302 or Q375 in VA387 affected binding to type O HBGA only, while switch mutants with three amino acid changes at either site from MOH to VA387 resulted in a weak binding to type O HBGAs. A further switch mutant with three amino acid changes at E378 from MOH to VA387 diminished the binding to type A HBGA only. Taken together, our data indicate that the binding pocket likely exists on NOR capsids. Direct evidence of this hypothesis requires crystallography studies.

scholarly journals Genetic Variation and Evolution of the 2019 Novel Coronavirus

2021 ◽  
pp. 1-13
Author(s):  
Salvatore Dimonte ◽  
Muhammed Babakir-Mina ◽  
Taib Hama-Soor ◽  
Salar Ali
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Rapid Evolution ◽  
Single Amino Acid ◽  
Angiotensin Converting Enzyme 2 ◽  
New Type ◽  
Amino Acid Mutations ◽  
Host Infection ◽  
Human Coronaviruses ◽  
Novel Coronavirus

<b><i>Introduction:</i></b> SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. <b><i>Methods:</i></b> This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. <b><i>Results:</i></b> The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. <b><i>Discussion/Conclusion:</i></b> Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

Structural assessment of single amino acid mutations: application to TP53 function

2006 ◽  
Vol 27 (9) ◽  
pp. 926-937 ◽  
Author(s):  
Yum L. Yip ◽  
Vincent Zoete ◽  
Holger Scheib ◽  
Olivier Michielin
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Structural Assessment ◽  
Amino Acid Mutations

Structural and functional consequences of single amino acid substitutions in the pyrimidine base binding pocket of Escherichia coli CMP kinase

FEBS Journal ◽  
2007 ◽  
Vol 274 (13) ◽  
pp. 3363-3373 ◽  
Author(s):  
Augustin Ofiteru ◽  
Nadia Bucurenci ◽  
Emil Alexov ◽  
Thomas Bertrand ◽  
Pierre Briozzo ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Binding Pocket ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Pyrimidine Base ◽  
Functional Consequences

scholarly journals Mutations in Plasmodium falciparumCytochrome b That Are Associated with Atovaquone Resistance Are Located at a Putative Drug-Binding Site

2000 ◽  
Vol 44 (8) ◽  
pp. 2100-2108 ◽  
Author(s):  
Michael Korsinczky ◽  
Nanhua Chen ◽  
Barbara Kotecka ◽  
Allan Saul ◽  
Karl Rieckmann ◽  
...  
Keyword(s):  
Amino Acid ◽  
Binding Site ◽  
Point Mutations ◽  
Drug Binding ◽  
Single Amino Acid ◽  
Malaria Parasites ◽  
Drug Binding Site ◽  
Sole Agent ◽  
Amino Acid Mutations

ABSTRACT Atovaquone is the major active component of the new antimalarial drug Malarone. Considerable evidence suggests that malaria parasites become resistant to atovaquone quickly if atovaquone is used as a sole agent. The mechanism by which the parasite develops resistance to atovaquone is not yet fully understood. Atovaquone has been shown to inhibit the cytochrome bc 1 (CYTbc 1) complex of the electron transport chain of malaria parasites. Here we report point mutations in Plasmodium falciparum CYT b that are associated with atovaquone resistance. Single or double amino acid mutations were detected from parasites that originated from a cloned line and survived various concentrations of atovaquone in vitro. A single amino acid mutation was detected in parasites isolated from a recrudescent patient following atovaquone treatment. These mutations are associated with a 25- to 9,354-fold range reduction in parasite susceptibility to atovaquone. Molecular modeling showed that amino acid mutations associated with atovaquone resistance are clustered around a putative atovaquone-binding site. Mutations in these positions are consistent with a reduced binding affinity of atovaquone for malaria parasite CYTb.

“GFP-Display,” an Easy Detection Method for Single Amino Acid Changes in a Target Polypeptide: Application to Random Mutagenesis

2002 ◽  
Vol 300 (1) ◽  
pp. 103-106 ◽  
Author(s):  
Takashi Aoki ◽  
Toshiyuki Tahara ◽  
Hiroyoshi Fujino ◽  
Hiroyuki Watabe
Keyword(s):  
Amino Acid ◽  
Detection Method ◽  
Random Mutagenesis ◽  
Single Amino Acid

Single amino acid mutations ofMedicagoglycosyltransferase UGT85H2 enhance activity and impart reversibility

FEBS Letters ◽  
2009 ◽  
Vol 583 (12) ◽  
pp. 2131-2135 ◽  
Author(s):  
Luzia V. Modolo ◽  
Luis L. Escamilla-Treviño ◽  
Richard A. Dixon ◽  
Xiaoqiang Wang
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Amino Acid Mutations ◽  
Enhance Activity

scholarly journals Functional analysis of single amino-acid mutations in the thrombopoietin-receptor Mpl underlying congenital amegakaryocytic thrombocytopenia

2008 ◽  
Vol 141 (6) ◽  
pp. 808-813 ◽  
Author(s):  
Marloes R. Tijssen ◽  
Franca di Summa ◽  
Sonja van den Oudenrijn ◽  
Jaap Jan Zwaginga ◽  
C. Ellen van der Schoot ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Amino Acid ◽  
Single Amino Acid ◽  
Thrombopoietin Receptor ◽  
Amino Acid Mutations

scholarly journals Positive and Negative Regulation of Poly(A) Nuclease

2004 ◽  
Vol 24 (12) ◽  
pp. 5521-5533 ◽  
Author(s):  
David A. Mangus ◽  
Matthew C. Evans ◽  
Nathan S. Agrin ◽  
Mandy Smith ◽  
Preetam Gongidi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Interactions ◽  
Binding Pocket ◽  
Negative Regulation ◽  
Single Amino Acid ◽  
Carboxy Terminus ◽  
Protein Protein Interactions ◽  
C Terminus

ABSTRACT PAN, a yeast poly(A) nuclease, plays an important nuclear role in the posttranscriptional maturation of mRNA poly(A) tails. The activity of this enzyme is dependent on its Pan2p and Pan3p subunits, as well as the presence of poly(A)-binding protein (Pab1p). We have identified and characterized the associated network of factors controlling the maturation of mRNA poly(A) tails in yeast and defined its relevant protein-protein interactions. Pan3p, a positive regulator of PAN activity, interacts with Pab1p, thus providing substrate specificity for this nuclease. Pab1p also regulates poly(A) tail trimming by interacting with Pbp1p, a factor that appears to negatively regulate PAN. Pan3p and Pbp1p both interact with themselves and with the C terminus of Pab1p. However, the domains required for Pan3p and Pbp1p binding on Pab1p are distinct. Single amino acid changes that disrupt Pan3p interaction with Pab1p have been identified and define a binding pocket in helices 2 and 3 of Pab1p's carboxy terminus. The importance of these amino acids for Pab1p-Pan3p interaction, and poly(A) tail regulation, is underscored by experiments demonstrating that strains harboring substitutions in these residues accumulate mRNAs with long poly(A) tails in vivo.

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