Peptidylprolyl cis/trans isomerases (immunophilins): Biological diversity targets - Functions

被引:309
作者
Galat, A [1 ]
机构
[1] CE Saclay, CEA, DSV, Dept Ingn & Etud Prot, F-91191 Gif Sur Yvette, France
关键词
D O I
10.2174/1568026033451862
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Information recovered from genome sequencing projects, multiple sequence alignments, structural analyses of PPIase and published records were used in deciphering the biological diversity, functions and targets of four groups of proteins encoded by dissimilar sets of sequences whose spatial representations exhibit peptidylprolyl cis/trans isomerase activity (PPIase). In the human genome there are encoded fifteen proteins whose segments have significant homology with the sequence of 12 kDa protein which is the target of the potent immunosuppressive macrolides FK506 or rapamycin. The 12 kDa archetype of the FK506-binding protein (FKBP), known as FKBP-12a, is an abundant intracellular protein whereas other FKBPs possessing from one to four FK506 like binding domains (FKBDs) have nominal masses varying from 13 to 135 kDa. The human genome contains at least sixteen genes encoding proteins comprising one cyclosporin-A (CsA) binding domain (CLD) called cyclophilins whose nominal masses vary from 17 to 324 kDa and multiple coding segments for small cyclophilins (17-19 kDa) whose transcription levels and functions remain unknown. The third group of PPIases encoded in the genome comprises two proteins (hPin1 and hParv14) where hPin1 is an important PPlase for cell cycle. The A thaliana, C. elegans, D. melanogaster and S. cerevisiae genomes encode a less diverse spectrum of PPIases whereas the prokaryotic genomes contain from none to three cyclophilins, from none to four genes encoding FKBPs, one distant homologue of the Pin1 protein named parvulin and the fourth group of PPIases known as trigger factors. PPIases are discretely distributed to different cellular compartments and interact with a number of targets that control a,range of cellular processes. Analyses of the sequence alignments of the two groups of PPIases, namely cyclophilins and FKBPs from diverse phyla, show that in each group their sequences diverge but the amino acid residues which form the PPIase activity site and macrolide binding cavity remain well conserved in the majority of them which suggests that the spatial structures and functions of each group of PPIases remain conserved.
引用
收藏
页码:1315 / 1347
页数:33
相关论文
共 198 条
[1]   The genome sequence of Drosophila melanogaster [J].
Adams, MD ;
Celniker, SE ;
Holt, RA ;
Evans, CA ;
Gocayne, JD ;
Amanatides, PG ;
Scherer, SE ;
Li, PW ;
Hoskins, RA ;
Galle, RF ;
George, RA ;
Lewis, SE ;
Richards, S ;
Ashburner, M ;
Henderson, SN ;
Sutton, GG ;
Wortman, JR ;
Yandell, MD ;
Zhang, Q ;
Chen, LX ;
Brandon, RC ;
Rogers, YHC ;
Blazej, RG ;
Champe, M ;
Pfeiffer, BD ;
Wan, KH ;
Doyle, C ;
Baxter, EG ;
Helt, G ;
Nelson, CR ;
Miklos, GLG ;
Abril, JF ;
Agbayani, A ;
An, HJ ;
Andrews-Pfannkoch, C ;
Baldwin, D ;
Ballew, RM ;
Basu, A ;
Baxendale, J ;
Bayraktaroglu, L ;
Beasley, EM ;
Beeson, KY ;
Benos, PV ;
Berman, BP ;
Bhandari, D ;
Bolshakov, S ;
Borkova, D ;
Botchan, MR ;
Bouck, J ;
Brokstein, P .
SCIENCE, 2000, 287 (5461) :2185-2195
[2]   FKBP12, the 12-kDa FK506-binding protein, is a physiologic regulator of the cell cycle [J].
Aghdasi, B ;
Ye, KQ ;
Resnick, A ;
Huang, A ;
Ha, HC ;
Guo, X ;
Dawson, TM ;
Dawson, VL ;
Snyder, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2425-2430
[3]   Down-regulation of the stathmin/Op18 and FKBP25 genes following p53 induction [J].
Ahn, J ;
Murphy, M ;
Kratowicz, S ;
Wang, A ;
Levine, AJ ;
George, DL .
ONCOGENE, 1999, 18 (43) :5954-5958
[4]   SUBSTRATE-SPECIFICITY FOR THE HUMAN ROTAMASE FKBP - A VIEW OF FK506 AND RAPAMYCIN AS LEUCINE (TWISTED AMIDE) PROLINE MIMICS [J].
ALBERS, MW ;
WALSH, CT ;
SCHREIBER, SL .
JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (17) :4984-4986
[5]  
ALNEMRI ES, 1994, J BIOL CHEM, V269, P30828
[6]   A CONFORMATION OF CYCLOSPORINE-A IN AQUEOUS ENVIRONMENT REVEALED BY THE X-RAY STRUCTURE OF A CYCLOSPORINE-FAB COMPLEX [J].
ALTSCHUH, D ;
VIX, O ;
REES, B ;
THIERRY, JC .
SCIENCE, 1992, 256 (5053) :92-94
[7]   CONFORMATIONAL POLYMORPHISM OF CYCLOSPORINE-A [J].
ALTSCHUH, D ;
BRAUN, W ;
KALLEN, J ;
MIKOL, V ;
SPITZFADEN, C ;
THIERRY, LC ;
VIX, O ;
WALKINSHAW, MD ;
WUTHRICH, K .
STRUCTURE, 1994, 2 (10) :963-972
[8]   A CYCLOPHILIN-RELATED PROTEIN INVOLVED IN THE FUNCTION OF NATURAL-KILLER-CELLS [J].
ANDERSON, SK ;
GALLINGER, S ;
RODER, J ;
FREY, J ;
YOUNG, HA ;
ORTALDO, JR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (02) :542-546
[9]  
[Anonymous], 1986, NUMERICAL RECIPES FO
[10]   MOLECULAR-CLONING AND EXPRESSION OF A NOVEL HUMAN GENE THAT IS HIGHLY HOMOLOGOUS TO HUMAN FK506-BINDING PROTEIN 12KDA (HFKBP-12) AND CHARACTERIZATION OF 2 ALTERNATIVELY SPLICED TRANSCRIPTS [J].
ARAKAWA, H ;
NAGASE, H ;
HAYASHI, N ;
FUJIWARA, T ;
OGAWA, M ;
SHIN, S ;
NAKAMURA, Y .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 200 (02) :836-843