Chemoproteomic identification of a DPP4 homolog in Bacteroides thetaiotaomicron
Authors/Creators
- Keller, Laura J.1
-
Nguyen, Taylor H.1
- Liu, Lawrence2
- Hurysz, Brianna M.2
- Lakemeyer, Markus1
- Guerra, Matteo1
- Gelsinger, Danielle2
- Chanin, Rachael1
- Ngo, Nhi3
- Lum, Kenneth M.3
- Faucher, Franco1
- Ipock, Phillip1
- Niphakis, Michah J.3
- Bhatt, Ami S.1
- O'Donoghue, Anthony J.1
- Huang, Kerwyn Casey1
- Bogyo, Matthew1
- 1. Stanford University
- 2. University of California, San Diego
- 3. Lundbeck La Jolla Research Center, Inc., San Diego
Description
Serine hydrolases play important roles in signaling and human metabolism, yet little is known about their functions in gut commensal bacteria. Using bioinformatics and chemoproteomics, we identify serine hydrolases in the gut commensal Bacteroides thetaiotaomicron that are specific to the Bacteroidetes phylum. Two are predicted homologs of the human protease dipeptidyl peptidase 4 (hDPP4), a key enzyme that regulates insulin signaling. Functional studies reveal that BT4193 is a true homolog of hDPP4 that can be inhibited by FDA-approved type 2 diabetes medications targeting hDPP4, while the other is a misannotated proline-specific triaminopeptidase. We demonstrate that BT4193 is important for envelope integrity and that loss of BT4193 reduces B. thetaiotaomicron fitness during in vitro growth within a diverse community. However, neither function is dependent on BT4193 proteolytic activity, suggesting a scaffolding or signaling function for this bacterial protease.
Files
Files
(94.6 kB)
| Name | Size | Download all |
|---|---|---|
|
md5:635a8379b451c926daabf3bdea44c696
|
354 Bytes | Download |
|
md5:804f6cfafe753a2a2071b4e28ea23a66
|
1.9 kB | Download |
|
md5:903d331040681a9eb1956800367d68a2
|
505 Bytes | Download |
|
md5:515c962164b5a09d24b5ab847a9ec98f
|
267 Bytes | Download |
|
md5:4aa1eca743abad88845385237847406b
|
25.6 kB | Download |
|
md5:57960cf5d13cead2f1e291d1288bccb2
|
5.8 kB | Download |
|
md5:13a440c661085bdb6ed0b3d517e23601
|
2.1 kB | Download |
|
md5:b127528de356237220250d237641ae9d
|
168 Bytes | Download |
|
md5:64ef366b2dd4f7e5e95b305e7de072c1
|
2.9 kB | Download |
|
md5:6a1560583c1e1d27e34d9015aa37d343
|
170 Bytes | Download |
|
md5:85cb7f8591268c34e956191b7b1cd9ba
|
908 Bytes | Download |
|
md5:43db8f557c41c260fe0daff04f910c94
|
4.0 kB | Download |
|
md5:863a92befec994181a96305537b81d52
|
368 Bytes | Download |
|
md5:77a0ca95c451be5f365ba9551cf5ca53
|
1.4 kB | Download |
|
md5:4e1229ec172da9618a20db6c07a7cc2d
|
158 Bytes | Download |
|
md5:225ed7bdacfe73a61634f58dd495f570
|
361 Bytes | Download |
|
md5:eb8fd41401e7c61b1af223196bd15d89
|
2.6 kB | Download |
|
md5:d314b6649f4fb06b6d0c9e5cd608b8cd
|
1.4 kB | Download |
|
md5:e4b868f510f7d340e81c4747cafe5b2d
|
1.4 kB | Download |
|
md5:9265a8484ae2eee7d5b19200f7319417
|
4.9 kB | Download |
|
md5:40dd8dc4155cb0bc5fff7f3ea7b8a144
|
4.8 kB | Download |
|
md5:be48cabb5f8c109a90457054e0092a15
|
950 Bytes | Download |
|
md5:62ea0a61de0862647f681b4d24826e0f
|
290 Bytes | Download |
|
md5:5f3ebf17aa65da2f0424c1416c5eaeda
|
879 Bytes | Download |
|
md5:8cf5779883ec51fcb269e7eac9955837
|
899 Bytes | Download |
|
md5:2f71685074eefb9921af2058004a3985
|
209 Bytes | Download |
|
md5:9c26ba32b6b3efc77c7c1ba696443c91
|
1.3 kB | Download |
|
md5:7fc20467b2d14098db23edb6873be767
|
3.4 kB | Download |
|
md5:05c82a841443766c618e8279f1b69ed4
|
238 Bytes | Download |
|
md5:897349eb97d5d9f5b66e55fe018fbd08
|
199 Bytes | Download |
|
md5:41197f8e55c3e5460fd22b4d5343de43
|
24.2 kB | Download |