Amino acid substitution reveals the role of V-shape helix on construction of yeast carboxypeptidase Y

The major virulence determinant of the rodent malaria parasite,Plasmodium yoelii, has remained unresolved since the discovery of the lethal line in the 1970s. Because virulence in this parasite correlates with the ability to invade different types of erythrocytes, we evaluated the potential role of the parasite erythrocyte binding ligand,PyEBL. We found 1 amino acid substitution in a domain responsible for intracellular trafficking between the lethal and nonlethal parasite lines and, furthermore, that the intracellular localization ofPyEBL was distinct between these lines. Genetic modification showed that this substitution was responsible not only forPyEBL localization but also the erythrocyte-type invasion preference of the parasite and subsequently its virulence in mice. This previously unrecognized mechanism for altering an invasion phenotype indicates that subtle alterations of a malaria parasite ligand can dramatically affect host–pathogen interactions and malaria virulence.

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The Effects of Local Environments on the Pattern of Amino-Acid Substitution in Homologous Prote Instructures: the Role of Side-Chain to Main-Chain Van Der Waals Interactions

Techniques in Protein Chemistry ◽

10.1016/b978-0-12-194710-1.50050-3 ◽

1994 ◽

pp. 405-412 ◽

Cited By ~ 1

Author(s):

Yvonne J. Edwards ◽

Mark S. Johnson ◽

David S. Moss ◽

Tom L. Blundell

Keyword(s):

Amino Acid ◽

Amino Acid Substitution ◽

Main Chain ◽

Van Der Waals ◽

Van Der Waals Interactions ◽

Side Chain ◽

Local Environments

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The Role of Amino Acid Substitution in HepT Toward Menaquinone Isoprenoid Chain Length Definition and Lysocin E Sensitivity in Staphylococcus aureus

Frontiers in Microbiology ◽

10.3389/fmicb.2020.02076 ◽

2020 ◽

Vol 11 ◽

Author(s):

Suresh Panthee ◽

Atmika Paudel ◽

Hiroshi Hamamoto ◽

Anne-Catrin Uhlemann ◽

Kazuhisa Sekimizu

Keyword(s):

Staphylococcus Aureus ◽

Amino Acid ◽

Chain Length ◽

Amino Acid Substitution

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splitGFP Technology Reveals Dose-Dependent ER-Mitochondria Interface Modulation by α-Synuclein A53T and A30P Mutants

Cells ◽

10.3390/cells8091072 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1072 ◽

Cited By ~ 11

Author(s):

Tito Calì ◽

Denis Ottolini ◽

Mattia Vicario ◽

Cristina Catoni ◽

Francesca Vallese ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Substitution ◽

Mitochondrial Function ◽

Cell Metabolism ◽

Loss Of Function ◽

Function Mechanism ◽

Dose Dependent ◽

Familial Parkinson’S Disease ◽

Interface Modulation

Familial Parkinson’s disease (PD) is associated with duplication or mutations of α-synuclein gene, whose product is a presynaptic cytosolic protein also found in mitochondria and in mitochondrial-associated ER membranes. We have originally shown the role of α-syn as a modulator of the ER-mitochondria interface and mitochondrial Ca2+ transients, suggesting that, at mild levels of expression, α-syn sustains cell metabolism. Here, we investigated the possibility that α-syn action on ER-mitochondria tethering could be compromised by the presence of PD-related mutations. The clarification of this aspect could contribute to elucidate key mechanisms underlying PD. The findings reported so far are not consistent, possibly because of the different methods used to evaluate ER-mitochondria connectivity. Here, the effects of the PD-related α-syn mutations A53T and A30P on ER-mitochondria relationship were investigated in respect to Ca2+ handling and mitochondrial function using a newly generated SPLICS sensor and aequorin-based Ca2+measurements. We provided evidence that A53T and A30P amino acid substitution does not affect the ability of α-syn to enhance ER/mitochondria tethering and mitochondrial Ca2+ transients, but that this action was lost as soon as a high amount of TAT-delivered A53T and A30P α-syn mutants caused the redistribution of α-syn from cytoplasm to foci. Our results suggest a loss of function mechanism and highlight a possible connection between α-syn and ER-mitochondria Ca2+ cross-talk impairment to the pathogenesis of PD.

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A New Mutation in PlantALSConfers Resistance to Five Classes of ALS-Inhibiting Herbicides

Weed Science ◽

10.1614/ws-06-082.1 ◽

2007 ◽

Vol 55 (2) ◽

pp. 83-90 ◽

Cited By ~ 89

Author(s):

Cory M. Whaley ◽

Henry P. Wilson ◽

James H. Westwood

Keyword(s):

Amino Acid ◽

Amino Acid Substitution ◽

Acetolactate Synthase ◽

Single Nucleotide ◽

Whole Plant ◽

History Of ◽

Als Inhibitor ◽

Herbicide Use ◽

Smooth Pigweed

Experiments were conducted to evaluate a biotype of smooth pigweed that had survived applications of sulfonylurea (SU) and imidazolinone (IMI) herbicides in a single season. The source field had a history of repeated acetolactate synthase (ALS)-inhibiting herbicide use over several years. Whole-plant response experiments evaluated the resistant (R11) biotype and an ALS-inhibitor susceptible (S) smooth pigweed biotype to herbicides from the SU, IMI, pyrimidinylthiobenzoate (PTB), and triazolopyrimidine sulfonanilide (TP) chemical families. The R11 biotype exhibited 60- to 3,200-fold resistance to all four ALS-Inhibiting herbicide chemistries compared with the S biotype. Nucleotide sequence comparison ofALSgenes from R11 and S biotypes revealed a single nucleotide difference that resulted in R11 having an amino acid substitution of aspartate to glutamate at position 376, as numbered relative to the protein sequence of mouseearcress. This is the first report of an amino acid substitution at this position of anALSgene isolated from a field-selected weed biotype. To verify the role of this mutation in herbicide resistance, theALSgene was cloned and expressed inArabidopsis. TransgenicArabidopsisexpressing thisALSgene exhibited resistance to SU, IMI, PTB, TP, and sulfonylaminocarbonyltriazolinone ALS-Inhibiting herbicide classes.

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Governing the monomer-dimer ratio of human cystatin c by single amino acid substitution in the hinge region.

Acta Biochimica Polonica ◽

10.18388/abp.2009_2480 ◽

2009 ◽

Vol 56 (3) ◽

Cited By ~ 23

Author(s):

Aneta Szymańska ◽

Adrianna Radulska ◽

Paulina Czaplewska ◽

Anders Grubb ◽

Zbigniew Grzonka ◽

...

Keyword(s):

Amino Acid ◽

Cystatin C ◽

Amino Acid Substitution ◽

Mutational Analysis ◽

Three Dimensional ◽

Single Amino Acid Substitution ◽

Single Amino Acid ◽

Human Cystatin C ◽

Human Cystatin

Three dimensional domain swapping is one of the mechanisms involved in formation of insoluble aggregates of some amyloidogenic proteins. It has been proposed that proteins able to swap domains may share some common structural elements like conformationally constrained flexible turns/loops. We studied the role of loop L1 in the dimerization of human cystatin C using mutational analysis. Introduction of turn-favoring residues such as Asp or Asn into the loop sequence (in position 57) leads to a significant reduction of the dimer fraction in comparison with the wild type protein. On the other hand, introduction of a proline residue in position 57 leads to efficient dimer formation. Our results confirm the important role of the loop L1 in the dimerization process of human cystatin C and show that this process can be to some extent governed by single amino acid substitution.

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