Novel Membrane Protein Chaperone: Chloroplast SRP

Membrane proteins comprise ~35% of proteome and confer essential functionality to the cellular membrane. However, the biogenesis of membrane proteins poses enormous challenges to cellular protein homeostasis. Despite their importance, our understanding of molecular chaperones that handle membrane proteins lags far behind those for chaperones that handle soluble proteins such as Hsp70 and GroEL. Using the most abundant membrane protein on earth, the Light Harvesting Complex Protein (LHCP) family as model substrates, my lab discovered a novel chaperone, cpSRP43, that overcomes the aggregation and ensures the targeted delivery of LHCPs.

As an added bonus, we also discovered a novel ‘disaggregase’ activity of cpSRP43 that is driven by ATP-independent binding interactions with its substrates. Exploiting this system provides a unique opportunity to understand fundamental mechanisms for chaperones dedicated to membrane proteins, and to exploit their activity for biotechnology.

Selected Publications:

  • Jaru-Ampornpan P, Shen K, Lam VQ, Ali M, Doniach S, Jia TZ, and Shan SO. (2010) Nat. Struct. Mol. Biol. 17, 696-702. “ATP-independent reversal of a membrane protein aggregate by a chloroplast SRP subunit.” PMID: 20424608.
  • Nguyen, T.X., Jaru-Ampornpan, P., Lam, V.Q., Cao, P., Piszkiewicz, S., and Shan, S. (2013) J. Biol. Chem. “Mechanism of an ATP-independent protein disaggregase. I. Structure of a membrane protein aggregate reveals a mechanism of recognition by its chaperone.” PMID: 23525109.
  • Jaru-Ampornpan, P., Liang, F.C., Nisthal, A., Nguyen, T.X., Wang, P., Shen, K., Mayo, S.L., and Shan, S. (2013) J. Biol. Chem. “Mechanism of an ATP-independent protein disaggregase. II. Distinct molecular interactions drive multiple steps during aggregate disassembly.” PMID: 23519468.
  • Liang, F.-C., Kroon, G., McAvoy, C., Chi, C., Wright, P., and Shan, S.O. (2016) Proc. Natl. Acad. Sci. “Co-evolution of two GTPases enables efficient protein targeting in an RNA-less chloroplast Signal Recognition Particle pathway.” PMID: 26951662.
  • Chandrasekar S, Sweredoski MJ, Sohn CH, Hess S, Shan SO. (2016) J. Biol. Chem. “Conformational dynamics of a membrane protein chaperone enables spatially-regulated substrate capture and release.” PMID:27895118.
  • Chandrasekar S, Shan SO. (2016) J. Biol. Chem. “Anionic phospholipids and the Albino3 translocase activate SRP-receptor interaction during LHCP targeting.” PMID:27895124.