Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia

Research output: Contribution to journalArticle

Standard

Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia. / Vihinen, Mauno; ZVELEBIL, MJJM; ZHU, QL; BROOIMANS, RA; OCHS, HD; ZEGERS, BJM; NILSSON, L; WATERFIELD, MD; SMITH, CIE.

In: Biochemistry, Vol. 34, No. 5, 1995, p. 1475-1481.

Research output: Contribution to journalArticle

Harvard

Vihinen, M, ZVELEBIL, MJJM, ZHU, QL, BROOIMANS, RA, OCHS, HD, ZEGERS, BJM, NILSSON, L, WATERFIELD, MD & SMITH, CIE 1995, 'Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia', Biochemistry, vol. 34, no. 5, pp. 1475-1481. https://doi.org/10.1021/bi00005a002

APA

Vihinen, M., ZVELEBIL, MJJM., ZHU, QL., BROOIMANS, RA., OCHS, HD., ZEGERS, BJM., ... SMITH, CIE. (1995). Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia. Biochemistry, 34(5), 1475-1481. https://doi.org/10.1021/bi00005a002

CBE

Vihinen M, ZVELEBIL MJJM, ZHU QL, BROOIMANS RA, OCHS HD, ZEGERS BJM, NILSSON L, WATERFIELD MD, SMITH CIE. 1995. Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia. Biochemistry. 34(5):1475-1481. https://doi.org/10.1021/bi00005a002

MLA

Vancouver

Author

Vihinen, Mauno ; ZVELEBIL, MJJM ; ZHU, QL ; BROOIMANS, RA ; OCHS, HD ; ZEGERS, BJM ; NILSSON, L ; WATERFIELD, MD ; SMITH, CIE. / Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia. In: Biochemistry. 1995 ; Vol. 34, No. 5. pp. 1475-1481.

RIS

TY - JOUR

T1 - Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia

AU - Vihinen, Mauno

AU - ZVELEBIL, MJJM

AU - ZHU, QL

AU - BROOIMANS, RA

AU - OCHS, HD

AU - ZEGERS, BJM

AU - NILSSON, L

AU - WATERFIELD, MD

AU - SMITH, CIE

PY - 1995

Y1 - 1995

N2 - Deficiencies in a tyrosine kinase, designated Btk, cause X-linked agammaglobulinemia (XLA) in man, a hereditary defect of B-cell differentiation. Mutations in the newly found PH domain located at the N-terminus of Btk have been shown to be the direct cause of XLA, and here two new mutations, T33P and V64F, are presented. Btk is thus far the only protein in which mutations of the PH domain have been found to cause a disease. The three-dimensional structure of the Btk PH domain was modeled on the basis of the dynamin PH structure. Despite a relatively low sequence similarity the Btk PH domain seems to have the same two P-sheet structure observed in the known structures. The model was used to interpret the structural basis for disease in five independent point mutations and in an insertion in patients with XLA. The mutated residues F25, V64, and V113, and possibly residue(s) around Q103, could form a binding site, since these amino acids are located close to each other on the surface of the molecule.

AB - Deficiencies in a tyrosine kinase, designated Btk, cause X-linked agammaglobulinemia (XLA) in man, a hereditary defect of B-cell differentiation. Mutations in the newly found PH domain located at the N-terminus of Btk have been shown to be the direct cause of XLA, and here two new mutations, T33P and V64F, are presented. Btk is thus far the only protein in which mutations of the PH domain have been found to cause a disease. The three-dimensional structure of the Btk PH domain was modeled on the basis of the dynamin PH structure. Despite a relatively low sequence similarity the Btk PH domain seems to have the same two P-sheet structure observed in the known structures. The model was used to interpret the structural basis for disease in five independent point mutations and in an insertion in patients with XLA. The mutated residues F25, V64, and V113, and possibly residue(s) around Q103, could form a binding site, since these amino acids are located close to each other on the surface of the molecule.

U2 - 10.1021/bi00005a002

DO - 10.1021/bi00005a002

M3 - Article

VL - 34

SP - 1475

EP - 1481

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 5

ER -