The ConSurf Server
	Server for the Identification of Functional Regions in Proteins
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Click on the linked example titles to view ConSurf results and the rotatable molecules colored according to ConSurf conservations scores, or click on the static figures to see them in greater detail.

Example 1: MHC Class I Heavy Chain (H-2Kb, PDB ID 2VAA chain A). 
Complexed With Beta-2 Microglobulin (Chain B) and Vesicular Stomatitis Virus Nucleoprotein (fragment 52-59, chain P). 

Here, both variability and conservation reflect function. Functional variability is seen in the peptide-binding groove (Fig. MHC_1, accomodating chain P). Allelic diversity in the population, concentrated in the inner surface of the groove, enables the population to present the maximal range of foreign (e.g. viral) peptides to T lymphocytes, for defensive immune responses. Conserved patches suggest functions, some of which may not yet be identified. Gln226 is known to be important in binding the CD8 coreceptor of the T cell (Kern et al.). Conservation is also evident in the interface binding chain B (Fig. MHC_2). Fig. MHC_3 shows a general view of the Protein explorer graphic page.
More on MHC structure is at the Lehninger and Martz sites. 
 

Fig. MHC_1	Fig. MHC_2	Fig. MHC_3

Example 2: Potassium Channel (Kcsa, PDB ID 1bl8 chain A) 
Potassium Channel (Kcsa, chains: A, B, C, D) From Streptomyces Lividans 

The potassium channel is an integral membrane protein with sequence similarity to all known K+ channels, particularly in the pore region. In Fig. 1bl8_1, we can see a general view of the conservation pattern of one of the four identical subunits (chain A, all other subunits in strands, K+ atoms yellow), which shows that ConSurf clearly detects the conservation among the amino acids facing the pore region (critical K+ signature sequence aa). Fig. 1bl8_2, shows in greater detail the the contact between a K+ atom and the highly conserved G77, Y78 and G79 amino acids, which are known to be absolutely required for K+ selectivity. 
More on the the structure and function of the potassium channel at ( Doyle et al.) 
 

Fig. 1bl8_1	Fig. 1bl8_2

Example 3: Human Insulin (protein sequence and structure analysis) (INS_HUMAN) 

Proinsulin is the prohormone precursor to insulin made in the beta cell of the islets of Langerhans. In humans, proinsulin is encoded by the INS gene. Proinsulin is processed by a series of proteases to form mature insulin. During this process the Signal peptide (1-24) and the C peptide (57-87) are removed. The remaining peptides (Insulin A Chain and Insulin B chain) are connected by disulfide bonds and constitute the mature insuline. In figure INS_HUMAN (located below) the ConSurf analysis for INS_HUMAN is shown. The figure reveal that the Insulin B (25-54) and Insulin A (90-110) peptides are highly conserved. In addition the disulfide bonds (CYS31-CYS96, CYS43-CYS109 and CYS95-CYS100) which are crucial to the structure of the mature insuline are also highly conserved compared to the removed peptides.  More about the human proinsulin at (Nicol et al),(Oyer et al.)  and (Ko et al).
In addition using the ConSurf result page the user can also review the projection of the conservation scores calculated for the sequence onto the insulin structures.
 

Fig. INS_HUMAN