HSP27: Species Variation
IHC staining of Hsp22 in mouse spinal cord sections (DAPI merged with Alexa 488) using Anti-Hsp22 (rabbit polyclonal)
The small Heat Shock protein (sHsp), Hsp27 (HspB1), belongs to the family of α-crystallin proteins and is present in both prokaryotic and eukaryotic organisms. Moreover, they participate on the maintenance of normal cell homeostasis and control during cellular stress. All vertebrates express multiple sHsps, which are important components of the cellular chaperoning machinery and display a great diversity of functions. This ranges from remodeling the cytoskeleton and inhibiting apoptosis to serving as structural proteins in eye lens and sperm tail41. Moreover, Hsp27 participates in the recycling of misfolded proteins (chaperone activity) and have a role on apoptosis and carcinogenic processes. Endoplasmic α-crystallins are widely distributed among all kingdoms, and their existence has been reported in numerous organisms from bacteria to humans. The number of genes coding for sHsps varies among species. For instance, only one sHSP gene has been located in yeast cells, ten in mammalian, two in birds and four genes have been found in Drosophila. The case in plants is more complicated since they have more than 20 sHSP genes. Thus, they are divided in 6 classes, of which, 3 classes (CI, CII and CIII) are in the cytosol or in the nucleus and the other three (CIV, CV and CVI) in the plastids25. It is noteworthy, however, that not all organisms contain α-Crystallins. Owing to the steadily growing number of whole-genome sequences, it is now possible to determine the exact number of α- Crystallins sHsp genes in a diverse array of organisms. For instance, Archea have genomes that encode one or two sHsps. Moreover, lateral gene transfer by bacterial donors explains the presence of dnaK, dnaJ, and grpE genes in archaea42. Thus, the universal occurrence of α -crystallins in the archaeal kingdom might be indicative of an early phylogenetic origin of this protein family43. Thermophilic archea and bacteria thermophiles like Thermotoga maritima and Synechococcus vulcanus each contain a single sHsp gene. The complete absence of α-crystallin genes in a number of bacteria became evident during mining of genome-sequencing data. The minimal sHsp set consists of GroEL and GroES, DnaK, DnaJ and GrpE, ClpB, Lon, and FtsH. Both Mycoplasma species sequenced lack genes coding for ClpA, ClpP, ClpX, HtpG, DegP, and sHsps44.
Regulation of apoptosis by Hsp27, intrinsic and extrinsic pathways.
(From Mymrikov, E. V, Seit-Nebi, A. S. & Gusev, N. B. Large potentials of small heat shock proteins, (2011).58
On larger genomes, the more genes seem to be devoted to the adaptation to atypical conditions. It should be pointed out, however, that a small genome does not strictly coincide with the absence of α-crystallin sHsps. For instance, Buchnera sp. strain APS (0.64 Mb) and Rickettsia prowazekii (1.1 Mb) each carry an α-crystallin-type protein. Deducing the absence of these proteins from the limited genome size of these two species would have been misleading.
A more detailed investigation of B. japonicum extracts uncovered at least 10 heat-induced small proteins belonging to the α-crystallin family. On the basis of their primary amino acid sequence, the sHsps were tentatively divided into two classes, class A and class B45. Hsp27 is a Class A protein (like HspA, HspD, HspE, and HspH) are closely related to the E. coli IbpA and IbpB proteins (Figure 2). Class B α-crystallins (HspC and HspF) are distinguished from class A proteins by their much longer N-terminal region and a shorter C-terminal extension. They have little similarity to E. coli sHsps. Additional evidence for the presence of multiple sHsps and for the existence of distinct classes in rhizobia was provided by the determination of the entire genome sequence of Mesorhizobium loti and Sinorhizobium meliloti. Eight α-crystallin sHsp genes encoding four class A and four class B proteins were identified in the first organism, and five genes encoding three class A and two class B proteins were identified in the latter. In this respect, the situation in rhizobial cells is similar to that in plant cytosol, in which three classes of sHsps (class I, II, and III) have been described. α-crystallins are not the only rhizobial chaperones that are present in multiple copies. Several groESL operons or groEL genes were found not only in Rhizobium leguminosarum, S. meliloti, B. japonicum, and M. loti but also in many other microorganisms46,47,48,49.
Eukaryotes are well known for containing multiple α-crystallins. Saccharomyces cerevisiae inhabits the lower end of the scale with two α-Hsps (Hsp26 and Hsp42), whereas plants lie at the upper end. The Arabidopsis thaliana genome exhibits 19 α-Hsps.
Six families of plant α-Hsps can be distinguished based on their sequence similarities and their cellular localization. Three families (I, II, and III) reside in the cytosol; one is localized to the chloroplasts, one is localized to the mitochondria, and one is localized to the endoplasmic reticulum50,27. Nine human α-Hsps, including αA- and αB-crystallin, have been described48. Once thought to be eye lens specific proteins, mammalian α-crystallins have now been found in many cell types51. In contrast to plant α -Hsps, the mammalian family members seem to be restricted to the cytosol and to the nucleus and do not localize to other cellular compartments.
In vertebrates, multiple small heat shock proteins (sHsps) are expressed and are important components of the cellular chaperoning machinery and display a spectacular diversity of functions. Secondary structure predictions of orthologous sHsps from different vertebrate classes indicate conservation of the beta-sandwich structure of the functionally important C-terminal “alpha-crystallin domain,” while the N-terminal domains generally have alpha-helical structures, despite their pronounced sequence variation41,52. Most information is available for the 10 known mammalian sHsps, formally named HspB1-B10. Only three of them (Hsp27/B1, alphaA-crystallin/B4, alphaB-crystallin/B5) have been reported from non-mammalian vertebrates, while an apparent paralog, Hsp30/B11, is found in frogs and teleost fish.
Hsp27 in plants
Environmental stress in plants has a great impact in agricultural and economic development throughout the world. Thus intensive research to understand how plants cope with stress is of great necessity. In plants, environmental stresses like high light intensity, drought, extreme temperatures, heavy metals and UV radiations all enhance photosynthetic ROS generation53 and thus they too have evolved to cope with harmful conditions by activating several small Hsps genes. In plants, there are at least seven different plant sHSP subfamilies54. A minimum of three plant sHSP subfamilies localize to the cytosol. In addition, there are subfamilies that localize to the chloroplast (CP), mitochondria (MT), endoplasmic reticulum (ER), and peroxisome (PX), respectively. The exact timing of the origin of the plant sHSP subfamilies is not yet known. However, at least some subfamilies originated very early in land plant evolution as two of the cytosolic subfamilies and the CP subfamily have been identified in bryophytes55. Curiously, none of the organelle-localized plant sHSP subfamilies have homologs in animals, fungi, or even in green algae56,57.