Kim, MK Kim, ES Kim, DS Choi, IH Moon, T Yoon, CN Shin, JS 2024-01-21T06:10:40Z 2024-01-21T06:10:40Z 2021-09-05 2004-10-14 0925-4439 https://pubs.kist.re.kr/handle/201004/137137 Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and increased susceptibility of infections, with mutations of the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two novel mutations of WAS at T336C on exon 3, and at 1326-1329, a G deletion on exon 10, resulting in L101P missense mutation and frameshift mutation 444 stop, respectively, are reported. The affected patients with either mutation showed severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE-labeled T cells division. Because WASP L 101 have not shown direct nuclear Overhauser effect (NOE) contact with the WASP-interacting protein (WIP) in NMR spectroscopy, molecular modeling was performed to evaluate the molecular effect of WASP P101 to WIP peptide. It is presumed that P101 induced a conformational change in the Q99 residue of WASP and made the side chain of Q99 move away from the WIP peptide, resulting in disruption of the hydrogen bond between Q99 WASP and Y475 WIP. A possible model for the molecular pathogenesis of WAS has been proposed by analyzing the interactions of WASP and WIP using a molecular modeling study. (C) 2004 Elsevier B.V. All rights reserved. English ELSEVIER T-CELL-RECEPTOR ACTIN POLYMERIZATION GENE-MUTATIONS CUTTING EDGE WIP THROMBOCYTOPENIA ACTIVATION PHENOTYPE ORGANIZATION EXPRESSION Two novel mutations of Wiskott-Aldrich syndrome: the molecular prediction of interaction between the mutated WASP L101P with WASP-interacting protein by molecular modeling Article 10.1016/j.bbadis.2004.06.007 1 BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v.1690, no.2, pp.134 - 140 BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1690 2 134 140 scie scopus 000224518600005 2-s2.0-4644220799 Biochemistry & Molecular Biology Biophysics Cell Biology Biochemistry & Molecular Biology Biophysics Cell Biology Article T-CELL-RECEPTOR ACTIN POLYMERIZATION GENE-MUTATIONS CUTTING EDGE WIP THROMBOCYTOPENIA ACTIVATION PHENOTYPE ORGANIZATION EXPRESSION Wiskott-Aldrich syndrome (WAS) WAS protein (WASP) WASP-interacting protein (WASP) molecular modeling