Novel Modular Rhodopsins from Green Algae Hold Great Potential for Cellular Optogenetic Modulation Across the Biological Model Systems
Abstract
:1. Introduction
2. Materials and Methods
2.1. Identification of Rhodopsin Domain, Homology and Structural Analysis
2.2. Evolutionary Analysis of Rhodopsin Domains of Modular Proteins
2.3. Protein-Protein Interaction Analysis of Novel Domains from Modular Algal Rhodopsins
3. Results and Discussion
3.1. Microbial Rhodopsins With Modular Domain Organization
3.2. Modular Channelrhodopsins and Their Optogenetic Potential
3.3. Modular Sensory-Type Rhodopsins and Their Optogenetic Potential
3.4. Light-Gated Ion Pump and Photo-Sensory Function Prediction Based on Conserved Residues of Rhodopsins
3.5. Spectral Tuning of the New Microbial Rhodopsins
3.6. Evolutionary Pattern of the Modular Microbial Rhodopsins
3.7. Cyclase Domain is a Canonical Secondary Messenger of Modular Sensory Type Rhodopsin
3.8. Optogenetic Potential of the Novel Modular Rhodopsins
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
Cop-Chlamyopsin | rhodopsin from Chlamydomonas reinhardtii |
Vop-Volvoxopsin | rhodopsin from Volvox carteri |
GpRh 1−5 | rhodopsin from Gonium pectorale |
AsRh1−4 | Asterochloris sp. |
KnRh1−3 | Klebsormidium nitens |
OtRh1−2 | Ostreococcus tauri |
MpuRh1&2 | Micromonas pusilla |
MspRh1&2 | Micromonas species |
OlRh1−4 | Ostreococcus lucimarinus |
CsRh1 | Chlorella sorokiniana |
ApRh1 | Auxenochlorella protothecoides |
BgRh1&2 | Bigelowiella natans |
GtRh1−10 | Guillardia theta |
DsRh1 | Dunaliella salina |
TsRh1 | Tetraselmis subcordiformis |
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Modular Domain | Channelrhodopsin | Functional Role and Optogenetic Potential |
---|---|---|
FimV (Peptidoglycan binding protein) | KnRh3 | In bacteria: Controls bacterial pathogenesis by indirectly activating adenylyl cyclase and hence cAMP level. |
MED15 (Subunit of mediator complex) | TsRh1 | In mammals: Regulates cholesterol and lipid homeostasis. Promotes cancerous growth and is used as a biomarker for malignancies. |
UL36 (Large tegument protein) | GpRh1 | Regulates viral entry to the cells. |
Function of the Residue | Proton Acceptor | Proton Donor | DC Gate | Stabilizes Proton Acceptor | Retinal Attachment |
---|---|---|---|---|---|
No. corresponds to ChR2 | 253 | 156 | 128 | 120 | 257 |
ChR2 | D253 | D156 | C128 | R120 | K257 |
KnRh3 | D250 | D154 | C126 | R118 | K254 |
TsRh1 | D236 | D139 | C111 | R103 | K240 |
GpRh1 | D213 | D116 | C88 | R80 | K217 |
Modular Domain | Modular Rhodopsins | Cellular Role and Optogenetic Potential |
---|---|---|
HisK | DsRh1, GtRh4-10, Cop5-12, Vop5-8, AsRh1-3, GpRh2-5, KnRh1 & 2, OtRh1&2, OlRh1-4, MpuRh1&2, Msp1&2, CsRh1, ApRh1, BgRh1&2 | Part of two-component signaling; regulates gene expression |
HisK-RR (Histidine kinase-response regulator) Two-component signaling system | GtRh4-8, Cop5-12, Vop5-8, AsRh1-3, GpRh2-5, KnRh1 & 2, OtRh1&2, OlRh1-4, MpuRh1&2, Msp1&2, CsRh1, ApRh1, BgRh1&2 | Regulates gene expression and various other cell processes via output domain like helix-turn-helix (HTH), RNA, enzyme, or ligand-binding domain. |
Cyc (Cyclase) | Cop5, 6, 8, 9 &10, Vop6&8, AsRh1-3, GpRh3&4, KnRh1 & 2 | Regulates the level of secondary messengers: cAMP and cGMP. |
SMC_N (Structural Maintenance of chromosome _N terminal) | Cop5, Vop5, GpRh4 | Stabilizes the chromosome, helps in its proper segregation during cell division and DNA repair. |
Tnp (Transposase) | Cop9 & 10 | Recognizes the transposable elements in DNA and catalyzes their movement to another DNA. |
SAM (Sterile alpha motif) | Cop5-8, Vop5, KnRh1 & 2 | Mediate protein-protein interactions, RNA and lipid binding; regulates transcription factor |
ICP4 (Infected-cell polypeptide 4) | KnRh1 | Major transcription factor of herpes simplex virus type1 (HSV-1) |
Mn104 (Microneme/rhoptry) | KnRh1 | Helps in invading host cell by apicomplexan parasites; N-terminal region proposed to serve as a signal peptide for ER |
MotB (Flagellar motor protein) | KnRh2 | MotB acts as a stator in the proton pump. |
RPT1 (Regulatory Particle Triple ATPase) | GpRh5 | Forms a part of 26S proteasomal complex |
BRD (Bromodomain) | GpRh5 | Modulate gene expression by associating with acetylated lysine on histone |
TPR (Tetracopeptide repeat) | OtRh2 | Regulates virulence in bacteria; translocation of receptors to their respective organelles in different systems |
SPRY [Spore lysis A (Spl A) in Dictyostelium discoideum and mammalian Ryanodine receptor (RYR)] | GtRh1 | Substrate binding for ubiquitination in ubiquitin ligase family proteins; involved in the various immune response |
DUF (Domain of unknown function) | GtRh1 | Mediate protein-protein interaction and transcription repression; ATP dependent protein kinase; enzymatic part of dicer; virulence and pathogenesis. |
Rav1 (Regulator of V-ATPase of vacuole membrane protein 1) | AsRh4 | Regulates the assembly of V-ATPase (ATP powered H+ pump in vacuole forming organelles) |
WD40 | AsRh4 | Mediate protein–protein interaction |
Function of the Residue | Ion Pumping | Proton-Release to Outside | Retinal Attachment | |||||
---|---|---|---|---|---|---|---|---|
No. corresponds to BR | 85 | 89 | 90 | 96 | 212 | 194 | 204 | 216 |
BR | D | T | T | D | D | E | E | K |
HR | T90 | S94 | T95 | A101 | D217 | E198 | T209 | K221 |
KR2 (Na+) | N112 | D116 | V117 | Q123 | D251 | L227 | R243 | K255 |
ASR1 | D75 | T79 | T80 | S86 | P206 | S188 | D198 | K210 |
SR2 | D75 | T79 | T80 | F86 | D201 | L188 | D193 | K205 |
RhoGC | E254 | T258 | C259 | L265 | D380 | S364 | A372 | K384 |
RhoPDE | E164 | T168 | C167 | W175 | D292 | Q276 | G284 | K296 |
AsRh4 | D2593 | T2597 | T2598 | D2604 | D2718 | G2701 | E2710 | K2722 |
GtRh1 | F152 | S156 | T157 | I163 | D297 | G280 | K289 | K301 |
GtRh2/3 | D95 | T99 | C100 | T106 | D248 | T232 | E240 | K252 |
Cop5 | M113 | T117 | T118 | L124 | D239 | M223 | E231 | K243 |
Cop6 | Q170 | T174 | T175 | I181 | N294 | V279 | - | K298 |
Cop7 | Q161 | S165 | T166 | M172 | D287 | W271 | E279 | K291 |
Cop8 | L67 | T71 | A72 | I78 | D194 | D178 | S186 | K198 |
Cop9-10 | L141 | T145 | A146 | I152 | D268 | D252 | S260 | K272 |
Cop11 | C95 | T99 | T100 | L106 | D279 | L263 | E271 | K283 |
Cop12 | C95 | T99 | T100 | L106 | D221 | L205 | E213 | K225 |
Vop5 | M157 | T161 | T162 | L168 | D283 | L267 | E275 | K287 |
Vop6 | Q153 | T157 | T158 | I164 | N278 | L263 | - | K282 |
Vop7 | Q147 | S151 | T152 | M158 | D272 | W256 | E264 | K276 |
MspRh1 | E140 | T144 | T145 | I151 | D284 | F268 | Q276 | K288 |
MspRh2 | E142 | G146 | T147 | L153 | D299 | S283 | L291 | K303 |
MpuRh1 | E140 | T144 | T145 | I151 | D300 | F284 | Q292 | K304 |
MpuRh2 | S151 | S155 | T156 | L162 | D328 | A312 | A320 | K332 |
GtRh4 | Q92 | T96 | T97 | V103 | D225 | S209 | Y217 | K229 |
GtRh5 | Q222 | T226 | T227 | V233 | D355 | G339 | Y347 | K359 |
GtRh6 | Q234 | T238 | T239 | V245 | D367 | G351 | Y359 | K371 |
GtRh7 | Q116 | T120 | T121 | V127 | D249 | S233 | Y241 | K253 |
GtRh8 | Q226 | T230 | T231 | V237 | D359 | L343 | Y351 | K363 |
GtRh9 | Q229 | T233 | T234 | I240 | D362 | L346 | Y354 | K366 |
GtRh10 | Q192 | T196 | T197 | V203 | D325 | L309 | F317 | K329 |
BgRh1/2 | E173 | T177 | T178 | S184 | D302 | L286 | E294 | K306 |
OtRh1 | E181 | T185 | T186 | L192 | D314 | M298 | E306 | K318 |
OtRh2 | E476 | T480 | T481 | L487 | D609 | M593 | E601 | K613 |
OlRh1 | E204 | T208 | T209 | L215 | D337 | L321 | E329 | K341 |
OlRh2 | E260 | T264 | T265 | L271 | D393 | L377 | E385 | K397 |
OlRh3 | E188 | T192 | T193 | L199 | D321 | L305 | E313 | K325 |
OlRh4 | E115 | T119 | T120 | L126 | D248 | L232 | E240 | K252 |
DsRh1 | Q140 | S144 | T145 | M151 | D268 | L252 | E260 | K272 |
GpRh2 | C91 | T95 | T96 | L102 | D217 | L201 | E209 | K221 |
GpRh3 | Q85 | T89 | T90 | I96 | N209 | A194 | - | K213 |
GpRh4 | M67 | T71 | T72 | L78 | D193 | L177 | E185 | K197 |
GpRh5 | Q1412 | S1416 | T1417 | M1423 | D1537 | L1521 | E1529 | K1541 |
CsRh1 | M144 | A148 | T149 | T155 | D269 | L253 | E261 | K273 |
ApRh1 | M67 | A71 | T72 | T78 | D192 | A176 | E184 | K196 |
AsRh1 | N122 | T126 | T127 | L133 | N248 | L232 | T240 | K252 |
AsRh2 | N123 | T127 | T128 | L134 | N249 | L233 | S241 | K253 |
AsRh3 | Q78 | T82 | T83 | V89 | N203 | L187 | C195 | K207 |
KnRh1 | Q166 | T170 | T171 | M177 | D292 | L276 | E284 | K296 |
KnRh2 | Q95 | T99 | T100 | L106 | E221 | T205 | E213 | K225 |
Rhodopsin | 105th Position/ Corresponding Amino Acid | Polar/Non-Polar aa | Green/Blue Shifted |
---|---|---|---|
Green PR | Leucine | Non-Polar | Green |
Blue PR | Glutamine | Polar | Blue |
KnRh3, TsRh1 and GpRh3 | Isoleucine | Non-polar | Green |
Cop8-12, GpRh2, ApRh1, AsRh2 | Isoleucine | Non-polar | Green |
MspRh1, MpuRh1, AsRh3-4, OtRh1-2, OlRh1-4, DsRh1, GtRh2,3 | Leucine | Non-polar | Green |
Cop5-7, Vop5-7, GpRh3-5, GtRh4-10, AsRh1, MspRh2, MpuRh2, CsRh1, BgRh1-2, KnRh1-2 | Methionine | Non-polar | Green |
GtRh1 | Aspartate | Acidic | unknown |
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Awasthi, M.; Sushmita, K.; Kaushik, M.S.; Ranjan, P.; Kateriya, S. Novel Modular Rhodopsins from Green Algae Hold Great Potential for Cellular Optogenetic Modulation Across the Biological Model Systems. Life 2020, 10, 259. https://doi.org/10.3390/life10110259
Awasthi M, Sushmita K, Kaushik MS, Ranjan P, Kateriya S. Novel Modular Rhodopsins from Green Algae Hold Great Potential for Cellular Optogenetic Modulation Across the Biological Model Systems. Life. 2020; 10(11):259. https://doi.org/10.3390/life10110259
Chicago/Turabian StyleAwasthi, Mayanka, Kumari Sushmita, Manish Singh Kaushik, Peeyush Ranjan, and Suneel Kateriya. 2020. "Novel Modular Rhodopsins from Green Algae Hold Great Potential for Cellular Optogenetic Modulation Across the Biological Model Systems" Life 10, no. 11: 259. https://doi.org/10.3390/life10110259