Cellular and Molecular Life Sciences

, Volume 67, Issue 20, pp 3467–3488

Molecular aspects of cyclophilins mediating therapeutic actions of their ligands

Review

Abstract

Cyclosporine A (CsA) is an immunosuppressive cyclic peptide that binds with a high affinity to 18 kDa human cyclophilin-A (hCyPA). CsA and its several natural derivatives have some pharmacological potential in treatment of diverse immune disorders. More than 20 paralogues of CyPA are expressed in the human body while expression levels and functions of numerous ORFs encoding cyclophilin-like sequences remain unknown. Certain derivatives of CsA devoid of immunosuppressive activity may have some potential in treatments of Alzheimer diseases, Hepatitis C and HIV infections, amyotrophic lateral sclerosis, congenital muscular dystrophy, asthma and various parasitic infections. Here, we discuss structural and functional aspects of the human cyclophilins and their interaction with various intra-cellular targets that can be under the control of CsA or its complexes with diverse cyclophilins that are selectively expressed in different cellular compartments. Some molecular aspects of the cyclophilins expressed in parasites invading humans and causing diseases were also analyzed.

Keywords

Cyclophilin PPIase Cyclosporine A Immunophilin Immunosuppression 

Supplementary material

18_2010_437_MOESM1_ESM.pdf (47 kb)
Multiple sequence alignments of the human CLDs (MSA19) (PDF 47 kb)
18_2010_437_MOESM2_ESM.pdf (490 kb)
MSA of 496 CLDs from various cyclophilins (MSA496) (PDF 490 kb)
18_2010_437_MOESM3_ESM.pdf (109 kb)
MSA496.out containing information on the aligned sequences. (PDF 108 kb)
18_2010_437_MOESM4_ESM.pdf (21 kb)
Mutations in the triads (MSA19) that contain crucial AA residues for PPIase activity and CsA-binding in hCyPA (PDF 21 kb)
18_2010_437_MOESM5_ESM.pdf (1.1 mb)
A high resolution image of Figure 4A (PDF 1151 kb)
18_2010_437_MOESM6_ESM.tif (1.4 mb)
Graph computed from the MSA496 (TIFF 1468 kb)
18_2010_437_MOESM7_ESM.pdf (50 kb)
Statistical distribution of AA-diads computed from the human genomic database. (PDF 50 kb)
18_2010_437_MOESM8_ESM.pdf (557 kb)
Statistical distribution of AA-triads computed from the human genomic database. (PDF 556 kb)
18_2010_437_MOESM9_ESM.pdf (63 kb)
Analyses of the X-ray structures of diverse cyclophilins from vertebrates and some parasites. (PDF 62 kb)
18_2010_437_MOESM10_ESM.pdf (28 kb)
Conservation levels of several different sequence motifs of hCyPA deduced from the MSA496. (PDF 27 kb)
18_2010_437_MOESM11_ESM.pdf (130 kb)
Some of the cyclophilins encoded in Helminths. (PDF 129 kb)
18_2010_437_MOESM12_ESM.pdf (141 kb)
Contains a list of molecular interactions of the complexes shown in Table 1. (PDF 141 kb)

Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  1. 1.SIMOPRO, Institute de Biologie et de Technologies de Saclay, DSV/CEAGif-sur-Yvette CedexFrance
  2. 2.Instituto Nacional de Parasitología “Dr. M. Fatala Chabén” ANLIS, C.G. MalbránBuenos AiresArgentina

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