Structural highlights
Disease
[SPAG1_HUMAN] Primary ciliary dyskinesia. The disease is caused by mutations affecting the gene represented in this entry.
Function
[SPAG1_HUMAN] May play a role in the cytoplasmic assembly of the ciliary dynein arms (By similarity). May play a role in fertilization. Binds GTP and has GTPase activity.[1] [2]
Publication Abstract from PubMed
Tetratricopeptide repeat domains, or TPR domains, are protein domains that mediate protein:protein interaction. As they allow contacts between proteins, they are of particular interest in transient steps of the assembly process of macromolecular complexes, such as the ribosome or the dynein arms. In this study, we focused on the first TPR domain of the human SPAG1 protein. SPAG1 is a multidomain protein that is important for ciliogenesis whose known mutations are linked to primary ciliary dyskinesia syndrome. It can interact with the chaperones RUVBL1/2, HSP70, and HSP90. Using protein sequence optimization in combination with structural and biophysical approaches, we analyzed, with atomistic precision, how the C-terminal tails of HSPs bind a variant form of SPAG1-TPR1 that mimics the wild-type domain. We discuss our results with regard to other complex three-dimensional structures with the aim of highlighting the motifs in the TPR sequences that could drive the positioning of the HSP peptides. These data could be important for the druggability of TPR regulators.
Optimizing the First TPR Domain of the Human SPAG1 Protein Provides Insight into the HSP70 and HSP90 Binding Properties.,Dermouche S, Chagot ME, Manival X, Quinternet M Biochemistry. 2021 Mar 19. doi: 10.1021/acs.biochem.1c00052. PMID:33739091[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin W, Zhou X, Zhang M, Li Y, Miao S, Wang L, Zong S, Koide SS. Expression and function of the HSD-3.8 gene encoding a testis-specific protein. Mol Hum Reprod. 2001 Sep;7(9):811-8. doi: 10.1093/molehr/7.9.811. PMID:11517287 doi:http://dx.doi.org/10.1093/molehr/7.9.811
- ↑ Zhang ML, Wang LF, Miao SY, Koide SS. Isolation and sequencing of the cDNA encoding the 75-kD human sperm protein related to infertility. Chin Med J (Engl). 1992 Dec;105(12):998-1003. PMID:1299558
- ↑ Dermouche S, Chagot ME, Manival X, Quinternet M. Optimizing the First TPR Domain of the Human SPAG1 Protein Provides Insight into the HSP70 and HSP90 Binding Properties. Biochemistry. 2021 Mar 19. doi: 10.1021/acs.biochem.1c00052. PMID:33739091 doi:http://dx.doi.org/10.1021/acs.biochem.1c00052
