Hamers-Casterman, C, Atarhouch, T, Muyldermans, S, Robinson, G, Hamers, C, Songa, E B, Bendahman, N, and Hamers, R (1993) Naturally occurring antibodies devoid of light chains. Nature 363, 446–448. 

The very first description of heavy chain only antibodies in Camelidae.

Desmyter, A, Transue, TR, Ghahroudi, MA, Thi, MH, Poortmans, F, Hamers, R, Muyldermans, S, and Wyns, L (1996) Crystal structure of a camel single-domain VH antibody fragment in complex with lysozyme. Nat. Struct. Biol.3, 803–811. 

The first structure of a nanobody in complex with an antigen.

Lauwereys, M, Arbabi, Ghahroudi M, Desmyter, A, Kinne, J, Holzer, W, De, Genst E, Wyns, L, Muyldermans, S (1998) Potent enzyme inhibitors derived from dromedary heavy-chain antibodies. EMBO J. 17, 3512–3120. 

This paper provides the first evidence that dromedary heavy-chain antibodies, in vivo-matured in the absence of light chains, are a unique source of inhibitory antibodies.

De Genst, E, Silence, K, Decanniere, K, Conrath, K, Loris, R & Wyns, L (2006) Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies. PNAS 103, 124586–4591. 

Pivotal study that describes the structural basis for the preference of nanobodies to bind cryptic epitopes such as enzyme active sites.

Loris R, Marianovsky I, Lah J, Laeremans T, Engelberg-Kulka H, Glaser G, Muyldermans S, Wyns L (2003)  Crystal structure of the intrinsically flexible addiction antidote MazE. J Biol Chem 278, 28252-28257. 

This paper reports the succesfull crystallization of an intrinsically unfolded protein. First 'de novo' structure ever solved using a Xaperone as a crystallization aid.

Spinelli S, Desmyter A, Verrips CT, de Haard HJ, Moineau S, Cambillau C (2006) Lactococcal bacteriophage p2 receptor-binding protein structure suggests a common ancestor gene with bacterial and mammalian viruses. Nat Struct Mol Biol 13, 85-89. 

 Other 'de novo' structure solved with a Xaperone.

Tereshko V, Uysal S, Koide A, Margalef K, Koide S, Kossiakoff AA (2008) Toward chaperone-assisted crystallography: protein engineering enhancement of crystal packing and X-ray phasing capabilities of a camelid single-domain antibody (VHH) scaffold. Protein Sci  17, 1175-1187. 

This paper reports a systematic study on the potential of Xaperones. It introduces shotgun Met scanning methodology to introduce additional Se-Met positions in crystallization chaperones.

Lam AY, Pardon E, Korotkov KV, Hol WG, Steyaert J (2009) Nanobody- aided structure determination of the EpsI:EpsJ pseudopilin heterodimer from Vibrio vulnificus. J Struct Biol 166, 8-15. 

A Xaperone was successfully used to determine the structure of parts of multiprotein complexes.

Korotkov KV, Pardon E, Steyaert J & Hol, WG  (2009) Crystal structure of the N-terminal domain of the secretin GspD from ETEC determined with the assistance of a nanobody. Structure 17, 255-265. 

A Xaperone was used to crystallize a two-domain protein with a flexible interdomain linker. The Xaperone induced an additional level of symmetry that reduces interdomain motions.

Rasmussen SGF, Choi H-jung, Fung JJ, Pardon E, Casarosa P, Chae PS, Devree BT, Rosenbaum DM, Thian FS, Kobilka TS, Schnapp A, Konetzki I, Sunahara RK, Gellman SH, Pautsch A, Steyaert J, Weis WI & Kobilka BK (2011) Structure of a nanobody-stabilized active state of the ß2 adrenoceptor. Nature 469, 175–180.    See also N&V 

A Xaperone was used to stabilize the active conformation of the ß2-adrenergic receptor and to solve its structure.

Domanska K, Vanderhaegen S, Srinivasan V, Pardon E & Dupeux F, Marquez JK, Giorgetti S, Stoppini M, Wyns L, Bellotti V, & Steyaert J (2011) Atomic structure of a nanobody-trapped domain-swapped dimer of an amyloidogenic β2-microglobulin variant. PNAS. Published online before print. 

A Xaperone was used to trap a structural intermediate along the amyloidosis pathway of β2-microglobulin.

Rasmussen SGF, DeVree BT, Zou Y, Kruse AC, Chung KY,Thian TS, Chae, PS, Pardon E, Calinski D, Mathiesen JM, Shah STA, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis W, Sunahara RK, Kobilka BK (2011) Crystal Structure of the ß2 Adrenergic Receptor-Gs protein complex. Nature, advanced publication online.

Structure of the first signaling complex solved by nanobody aided crystallography

Steyaert J, Kobilka BK. (2011) Nanobody stabilization of G protein-coupled receptor conformational states. Curr Opin Struct Biol  21, 567-572.  

Korotkov K.V., Johnson T.L., Jobling M.G., Pruneda J., Pardon E., Héroux, A., Turley, S., Steyaert, J., Holmes, R.K., Sandkvist, M., & Hol, W.G.J. (2011) Structural and Functional Studies on the Interaction of GspC and GspD in the Type II Secretion System. PLoS Pathog 7,  e1002228.

Westfield, G., Rasmussen, S.G.F, Su M., Dutta, S, DeVree, B.T., Chung, K.Y., Calinski, D., Velez-Ruiz, G., Oleskie, A.N., Pardon, E., Chae, P.S., Liu, T., Li, S., Woods Jr., V.L., Steyaert, J., Kobilka, B.K., Sunahara, R.K. & Skiniotis, G. (2011) Structural flexibility of the Gαs α-helical domain in the β2-adrenoceptor Gs complex. PNAS, advance online publication, doi:10.1073/pnas.1113645108