PROSITE documentation PDOC51796 [for PROSITE entry PS51796]MSS4 domain profile
MSS4 (mammalian suppressor of Sec4) is an evolutionarily highly conserved protein, which is expressed in all mammalian tissues. Although it was first proposed to function as a guanine exchange factor (GEF) for Rab GTPases, it was soon described as a quite inefficient GEF and was thus suggested to function rather as a chaperone, protecting nucleotide free Rabs from degradation, than as a GEF [1].
The structure of MSS4 revealed a mostly β fold stabilized by a Zn(2+) ion coordinated by cysteine residues from two CxxC motifs. The fold of the MSS4 domain consists of a central β sheet (βG-βK) flanked by a β hairpin (βB-βC) on one side and a small variable sheet on the other (see <PDB:1HXR>). A single Zn(2+) ion, coordinated by the thiol groups of cysteine residues from two CxxC motifs located in the βB-βC and βI-βJ loops, appears to play an important structural role by reinforcing the hydrophobic core formed by the βB-βC hairpin, the βG-βH loop, and the central β sheet [2,3,4].
The profile we developed covers the entire MSS4 domain.
Last update:April 2016 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Walter B.M. Nordhoff C. Varga G. Goncharenko G. Schneider S.W. Ludwig S. Wixler V. |
| Title | Mss4 protein is a regulator of stress response and apoptosis. | |
| Source | Cell Death Dis. 3:E297-E297(2012). | |
| PubMed ID | 22495352 | |
| DOI | 10.1038/cddis.2012.37 |
| 2 | Authors | Yu H. Schreiber S.L. |
| Title | Structure of guanine-nucleotide-exchange factor human Mss4 and identification of its Rab-interacting surface. | |
| Source | Nature 376:788-791(1995). | |
| PubMed ID | 7651540 | |
| DOI | 10.1038/376788a0 |
| 3 | Authors | Zhu Z. Dumas J.J. Lietzke S.E. Lambright D.G. |
| Title | A helical turn motif in Mss4 is a critical determinant of Rab binding and nucleotide release. | |
| Source | Biochemistry 40:3027-3036(2001). | |
| PubMed ID | 11258916 |
| 4 | Authors | Itzen A. Pylypenko O. Goody R.S. Alexandrov K. Rak A. |
| Title | Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4. | |
| Source | EMBO J. 25:1445-1455(2006). | |
| PubMed ID | 16541104 | |
| DOI | 10.1038/sj.emboj.7601044 |
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