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1

Identification of a novel protein encoded by third conserved gene within RAG locus

100%

Kasztura M., Miazek A., Cebrat M., Kisielow P.

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issue 1

177-181

EN

Recently, a third evolutionarily conserved gene, NWC, was discovered within the recombination activating gene (RAG) locus, known to contain the RAG1 and RAG2 genes. Here, we identify and characterize the murine endogenous NWC protein which has no homology to any known protein and is ubiquitously expressed. In the cell, the NWC protein which has been suggested to function as a transcriptional repressor, is found in the cytoplasm as well as in the nucleus.

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Degenerate specificity of PDZ domains from RhoA-specific nucleotide exchange factors PDZRhoGEF and LARG

76%

Smietana K., Kasztura M., Paduch M., Derewenda U., Derewenda Z., Otlewski J.

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2008

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vol. 55

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issue 2

269-280

EN

PDZ domains are ubiquitous protein-protein interaction modules which bind short, usually carboxyterminal fragments of receptors, other integral or membrane-associated proteins, and occasionally cytosolic proteins. Their role in organizing multiprotein complexes at the cellular membrane is crucial for many signaling pathways, but the rules defining their binding specificity are still poorly understood and do not readily explain the observed diversity of their known binding partners. Two homologous RhoA-specific, multidomain nucleotide exchange factors PDZRhoGEF and LARG contain PDZ domains which show a particularly broad recognition profile, as suggested by the identification of five diverse biological targets. To investigate the molecular roots of this phenomenon, we constructed a phage display library of random carboxyterminal hexapeptides. Peptide variants corresponding to the sequences identified in library selection were synthesized and their affinities for both PDZ domains were measured and compared with those of peptides derived from sequences of natural partners. Based on the analysis of the binding sequences identified for PDZRhoGEF, we propose a sequence for an 'optimal' binding partner. Our results support the hypothesis that PDZ-peptide interactions may be best understood when one considers the sum of entropic and dynamic effects for each peptide as a whole entity, rather than preferences for specific residues at a given position.

3

"Żelazne serce" - co wiemy, a czego nie wiemy?

76%

Kasztura M., Stugiewicz M., Kobak K., Banasiak W., Ponikowski P., Jankowska E.

Kosmos

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2014

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vol. 63

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issue 3

387-393

PL

Gospodarka żelazowa odgrywa fundamentalną rolę w homeostazie organizmu. Niedobór żelaza jest najczęstszym niedoborem pokarmowym na świecie i dotyczy około 1/3 populacji ogólnej, a u osób starszych i ze schorzeniami przewlekłymi jest jeszcze częstszy. Stąd zaburzenia gospodarki żelazowej prowadzą do dysfunkcji w obrębie wszystkich hematopoetycznych linii komórkowych (erytrocytów, komórek odpowiedzi immunologicznej i trombocytów), ale także wiążą się z upośledzeniem funkcjonowania m.in. kardiomiocytów czy miocytów mięśni szkieletowych zużywających znaczne ilości energii. Istnieje wiele nurtujących pytań w obszarze roli żelaza w patogenezie i progresji niewydolności serca. Choć męczliwości mięśni szkieletowych i nietolerancji wysiłku fizycznego w niewydolności serca towarzyszy niedobór żelaza, a suplementacja żelaza takim chorym poprawia funkcję mięśni szkieletowych, niejasne są dokładne mechanizmy tłumaczące te obserwacje kliniczne.

EN

Iron metabolism is fundamental for homeostasis of the whole organism. Iron deficiency is the most common nutritional deficiency worldwide that affects more than one-third of the global population, with the highest prevalence in older people and those with chronic diseases. Deregulation of iron metabolism leads to dysfunction not only in all of haematopoetic cell lines (erythrocytes, cells involved in immune response and thrombocytes), but also in cells of high energy demand, such as cardiomyocytes and skeletal myocytes. There are many issues that still need to be addressed in the field of pathogenesis and progression of heart failure. Although skeletal muscle fatigability and exercise intolerance in heart failure is assisted by iron deficiency, and iron supplementation improves muscle function, the exact mechanisms of these clinical observations remain unclear however.

4

Phage display of proteins

75%

Kościelska K., Kiczak L., Kasztura M., Wesołowska O., Otlewski J.

Acta Biochimica Polonica

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1998

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vol. 45

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issue 3

705-720

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Identification of a novel protein encoded by third conserved gene within RAG locus

Degenerate specificity of PDZ domains from RhoA-specific nucleotide exchange factors PDZRhoGEF and LARG

"Żelazne serce" - co wiemy, a czego nie wiemy?

Phage display of proteins